Luteal phase insufficiency is one of the most important aspect of fertility treatment . But due to lack of proper understanding many unwanted medications are prescribed . This ppt will give an idea on the best evidence based luteal phase support for an ivf cycle.
Ovarian Hyperstimulation Syndrome(OHSS), is a Rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy where a patient's ovaries become swollen and fluid builds up around her abdomen
Ovarian Hyperstimulation Syndrome(OHSS), is a Rare iatrogenic complication of ovarian stimulation occurring during the luteal phase or during early pregnancy where a patient's ovaries become swollen and fluid builds up around her abdomen
Recurrent pregnancy loss is a significant redroductive medical problem, influencing 2%–5% of couples. ... Throughout the years, proof based medications, for example, surgical correction of uterine abnormalities or asprin and heparin for antiphospholipid syndrome have improved the results for couples with repetitive pregnancy loss.
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
Invited Lecture delivered by Dr Sujoy Dasgupta in a CME, sponsored by Serum Institute of India Pvt Ltd in the Convocation Ceremony of Interns at Sagor Dutta Medical College
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 .
Uterus Transplantation Utx (obstetric and gynecology) D.A.B.M
Is the surgical procedure whereby a healthy uterus is transplanted into an organism of which the uterus is absent or diseased.
As part of normal mammalian sexual reproduction, a diseased or absent uterus does not allow normal embryonic implantation, effectively rendering the female infertile.
This phenomenon is known as Absolute Uterine Factor Infertility (AUFI).
Uterine transplant is a potential treatment for this form of infertility.
Uterus is a dynamic, complex organ. It is hugely blood-flow dependent.
More than 116,000 Number of men, women and children on the national transplant waiting list as of August 2017.
33,611 transplants were performed in 2016.
20 people die each day waiting for a transplant.
every 10 minutes another person is added to the waiting list.
Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period.
This Presentation is made by Dr.Laxmi Shrikhande
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
Recurrent pregnancy loss is a significant redroductive medical problem, influencing 2%–5% of couples. ... Throughout the years, proof based medications, for example, surgical correction of uterine abnormalities or asprin and heparin for antiphospholipid syndrome have improved the results for couples with repetitive pregnancy loss.
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
Invited Lecture delivered by Dr Sujoy Dasgupta in a CME, sponsored by Serum Institute of India Pvt Ltd in the Convocation Ceremony of Interns at Sagor Dutta Medical College
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 .
Uterus Transplantation Utx (obstetric and gynecology) D.A.B.M
Is the surgical procedure whereby a healthy uterus is transplanted into an organism of which the uterus is absent or diseased.
As part of normal mammalian sexual reproduction, a diseased or absent uterus does not allow normal embryonic implantation, effectively rendering the female infertile.
This phenomenon is known as Absolute Uterine Factor Infertility (AUFI).
Uterine transplant is a potential treatment for this form of infertility.
Uterus is a dynamic, complex organ. It is hugely blood-flow dependent.
More than 116,000 Number of men, women and children on the national transplant waiting list as of August 2017.
33,611 transplants were performed in 2016.
20 people die each day waiting for a transplant.
every 10 minutes another person is added to the waiting list.
Recurrent pregnancy loss (RPL), also referred to as recurrent miscarriage or habitual abortion, is historically defined as 3 consecutive pregnancy losses prior to 20 weeks from the last menstrual period.
This Presentation is made by Dr.Laxmi Shrikhande
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.
Role of LH supplementation in reproductive medicine - Aspire 2013Sankalp Singh
To add or not to add LH is a highly contentious issue.Here,i would be discussing role of LH supplementation in IVF cycle as per present day evidence.
Also,will be scrutinising the available studies for their reliability or lack of it.
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
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
Infertility affects as many as 10% of the couples, the causes, investigations and treatment with mention of management of fibroids and endometriosis has been done in the presentation.
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.
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.
Individualized ovarian stimulation protocols in IVF (1).pptxRaju Nair
Explaining the best protocol for ivf stimulation. How we can optimize the stimulation regimen to get adequate response and there by healthy baby is a challenge
The concept of folliculogensis is the most exclusive topic in understanding the ovulation induction regimens . In this ppt , trying to decode the physiological aspect of ovarian folliculogensis
Biostatistics is one of the most unavoidable area in the modern day practice of evidence based medicine . In the ppt , trying to give a glimpse on how a clinician should approach Biostatistics
Bio similar and innovators - the battle of the two is a long story . In this presentation am trying to explain the merits nd demerits of each with available evidence
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
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
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.
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
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
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.
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
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
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
1. Dr Raju Nair
Head – Fertility Unit
Mitera Hospital, Kottayam
Kerala, India
Luteal Phase Insufficiency
2. Dr.Raju Nair
Director & HOD Reproductive medicine
Mitera Hospital, Kottayam, Kerala
Education:
MBBS : Government medcial college, Kottayam, ( 94-99)
MS( OBG) : Armed forces medcial college ( AFMC), Pune 2004
Reproductive Medicine Fellowship: CMC, Vellore 2007
Member- ESHRE, ASRM,ISAR, FOGSI, IAGE,ACE,IMA,IFS, ASPIRE
Reviewer : Cochrane network- sub fertility group
Scientific achievements :
11 articles in Indexed Journal
3 national best papers
>200 scientific lectures in state and national level ,5 international level scientific lectures
Contributed many chapters in Textbook related to ART
Academic activities:
Course director – Fellowship in Reproductive Medicine, Mitera Hospital, FNB examiner
Area of Interest :
IVF lab quality control, PCOD, Minimal stimulation ART
3. • Luteal phase deficiency (LPD) has been described as a condition in
which
• endogenous progesterone is not sufficient to maintain a functional secretory
endometrium and allow normal embryo implantation and growth
6. Luteal phase in a natural cycle
• Which hormones seem to be crucial during the luteal phase in a
natural cycle
7. The role of LH in the luteal phase: Crucial
• Totally responsible for steroidogenic activity of the corpus luteum (Casper
and Yen, 1979)
• Upregulation of growth factors, VEGF-A, FGF2 (Sugino et al., 2004; Wang et al., 2002)
• Upregulation of cytokines involved in implantation (Licht et al., 2001)
• Stimulation of LH receptors in endometrium (Rao, 2001; Tesarik et al., 2003)
8. The role of progesterone
• Induces secretory transformation of the endometrium in the luteal
phase (Bourgain et al., 1990)
• Progesterone deficiency delays endometrial maturation (Dallenbach-Hellweg, 1984)
• Removal of CL prior to 7 weeks of gestation leads to pregnancy loss
(Csapo, 1972)
• Normal pregnancy was sustained when progesterone was given after
removal of CL (Csapo, 1973)
9. What happens normally…
• Corpus luteum - Initial support
• Once pregnancy begins, corpus luteum rescue and maintenance
require a series of well-known endocrine, paracrine and autocrine
actions.
• luteoplacental shift (onset of placental steroidogenesis) is around the seventh
gestational week
11. Luteal phase deficiency (LPD)
• A condition of insufficient progesterone exposure to maintain a normal
secretory endometrium and allow for normal embryo implantation and
growth
Obstet Gynecol Clin North Am. 2015 March ; 42(1): 135–151.
12. Luteal phase deficiency
• 1970s, the Norfolk group performed several studies on premature
onset of menses due to low progesterone concentrations in the luteal
phase, which they called luteal phase deficiency (Jones, 1991).
• Luteal phase deficiency is defined as a
• luteal phase shorter than 11 days
• a lag of more than 2 days in endometrial histological development
• low mid-luteal progesterone values <10 ng/ml
13. LPD
• Infertility
• First trimester Pregnancy loss
• Short cycles
• Premenstrual spotting
• Anorexia
• Starvation, and eating disorders
• Excessive exercise
• Stress
• Obesity and polycystic ovary syndrome
• Endometriosis
• Aging
• Inadequately treated 21-hydroxylase deficiency
• Thyroid dysfunction
• Hyperprolactinemia
• ART cycles
• Random cycles with or without stimulation
Controversy regarding the clinical
significance of LPD is due in part to
the lack of a reliable test to diagnose
this disorder.
Luteal phase deficiency has
purportedly been associated
LPD is only clinically relevant if it is consistently present in most cycles
14. Detecting Luteal Phase Insufficiency
• Serum progesterone level: <3 ng/ml
• Mid-luteal phase: At least 6.5 ng/ml and preferably 10 ng/ml or more
• Blood levels range from 2 to 40 ng/ml within a brief time period
• Random serum progesterone levels are difficult to interpret beyond
documenting ovulation
• Endometrial biopsy is no longer the gold standard for assessment of
endometrial maturation
There is no consensus on minimum serum progesterone
concentration that defines luteal function
Indian J Endocrinol Metab. 2013 Jan;17(1):44-9.
15. • IF DIAGNOSIS IS NOT POSSIBLE, IS TREATMENT
FOR LUTEAL INADEQUACY EVER APPROPRIATE?
16. TREATMENT FOR
LUTEAL
INADEQUACY
• The first approach to treatment of
potential luteal inadequacy is the
correction of any underlying condition.
• hypothalamic dysfunction, thyroid dysfunction,or
hyperprolactinemia
• Rest are all empiric
• to promote endometrial maturation
• to enhance endometrial receptivity
• to support implantation and development of
an early pregnancy.
• Strategies
• supplemental progesterone
• progesterone plus estrogen
• human chorionic gonadotropin (hCG)
17. LPD: Prevalence
• 5-10% pregnant women have prevalence of LPD
• 25-40% women with ‘Recurrent pregnancy lose’ have prevalence of
LPD
• 15-20% women with ‘Unexplained infertility’ have prevalence of LPD
19. Luteal phase defect in all stimulated cycles
• Schematic representation of
changes in luteal phase length
and progesterone profile
induced by ovarian
hyperstimulation for IVF (Macklon et al.,
2006)
20. Why in ART Cycles….
• Suppression of endogenous luteinizing hormone secretion during the luteal phase as a result of persistent pituitary
suppression by GnRH agonists.
• Supraphysiological levels of both estradiol and progesterone in the early luteal phase may lead to advanced development
of the endometrium, hence asynchrony between the embryo and the endometrium and decreased pregnancy rates in IVF
cycles.
• Duration of ovarian steroid production is shorter in stimulated cycles compared with that of natural cycles. Early menses
may prevent successful implantation due to abrupt decreases in serum concentrations of estradiol and progesterone in
ART cycles compared with those of natural cycles.
• The aspiration of the granulosa cells that surround the oocyte can interfere with the production of progesterone.
• LH levels are lowered by high steroid levels, These steroid levels are high because of the multiple corpora lutea,which
produce more steroids than in a natural cycle. This causes a negative feedback on the pituitary gland and lowers the LH
levels. In this way the length of the luteal phase is shortened (known as premature luteolysis) and the chances of
pregnancy are reduced.
23. Luteal Phase Events
Trophic alterations
• Alterations in LH secretion
• Decreased LH surge and luteal levels
• Systemic factors
• Factors acting upon corpus luteum
Intrinsic corpus luteum defects
• Specific cellular defects
• Large and small cell abnormalities
Intrinsic secretory endometrial defect
• Deficient number of progesterone receptors
24. Luteal Rescue Events
Trophic alterations
• Defective hCG stimulus
Intrinsic corpus luteum defects in early pregnancy
• Defective progesterone synthesis
Intrinsic endometrial defects
26. Progesterone deficiency in ARTs
• Progesterone important for early embryonic development
• Deficient progesterone responsible for
• Implantation failure
• Miscarriages and
• unsuccessful ARTs
• In ART procedures, iatrogenically low progesterone environment is
created
Practice Committee of the American Society for Reproductive Medicine. Fertil Steril. 2012 Nov;98(5):1112-1117.
Shah and Nagarajan. Indian J Endocrinol Metab. 2013 JanFeb;17(1): 44–49.
27. Implantation failure
• Luteal phase progesterone deficiency – one of the reasons of
implantation failure
• Progesterone insufficiency interferes with secretory transformation of
endometrium
• Up-regulation of pro-inflammatory cytokines is a risk factor
• Pro-inflammatory cytokines- IFN-γ and TNF-α
• Down-regulation of anti-inflammatory IL-4, IL-6 and IL-10
28. Progesterone link with immune system
Progesterone stimulates
the production of
progesterone-induced
blocking factor (PIBF)
and induces via the
cytokines a T-helper 2
response
Progesterone is essential for
the maintenance of pregnancy.
It is produced by the corpus luteum
until week 7–9, when the placenta takes
over this function
Progesterone
CD-8 + T cell
PIBF
Norwitz ER, et al. N Engl J Med 2001; 345(19): 1400-1408.
Szekeres-Bartho J, Wegmann TG. J Reprod Immunol 1996; 31(1-2): 81-95.
Szekeres-Bartho J. Int Rev Immunol 2002; 21(6): 471-495.
29. Th1-Th2 Paradigm
T helper cells = sub-group of lymphocytes
• Th1 cells
Pro-inflammatory cytokines
IL-2, TNFα, TNFβ, IFNγ
Cell-mediated immunity
• Th2 cell
Anti-inflammatory cytokines
IL-4, IL-5, IL-6, IL-10, IL-13
Humoral immunity
Th1 Th2
Cytokines
T Cell Immunology. Available from: http://www.bdbiosciences.com/research/tcell/about/helper.jsp. (last accessed February 2014).
Raghupathy R, et al. BJOG 2005; 112(8): 1096-1101.
30. Decreased survival of embryo due to
hyper immunity
Progesterone
PIBF
Normally
Progressing
Pregnancy
Progesterone
PIBF
Miscarriage
Mifepristone
Progesterone
PIBF
+anti-PIBF
Miscarriage
Adapted from: Szekeres-Bartho J, et al. Int Immunopharmacol 2001; 1(6): 1037-1048.
31. Role of Human chorionic gonadotropin
• Human chorionic gonadotropin (HCG) acts as indirect support of
luteal support
• HCG stimulates corpus luteum
• Increases the concentration of estrogen and progesterone – rescues
failing corpora lutea
• Administration of HCG icreases placental protein 14, integrin and
relaxin
• HCG insufficiency may lead to miscarriage
Hutchinson-Williams et al. Fertil Steril. 1990;53:495–501.
Anthoy et al. Fertil Steril. 1993;59:187–91.
Ghosh et al. Hum Reprod. 1997;12:914–20.
32. Role of HCG in human pregnancy
Adapted from: Polese et al. Front. Endocrinol. 2014; 5:106.
34. What is Evidence-Based
Medicine?
• “The integration of individual clinical expertise with the
best available clinical evidence from systematic
research.”
• David L Sackett, W Scott Richardson, William
Rosenberg, R Brian Haynes Evidence Based Medicine--
How to Practice and Teach EBM, 1996
14 March 2023 34
35. • There is a worldwide controversy concerning the
• Requirement of luteal phase support
• Type of hormones used for LPS
• Dose and duration
• When to start
• When to stop
37. Normal cycle
• Role of luteal phase support
• Normo ovulatory patient
• PCOD
• Prevent miscarriage
• No treatment for luteal phase insufficiency has been shown to
improve pregnancy outcomes in natural, unstimulated cycles.
38. non-ART cycle
• Use of supplemental progesterone, in a non-ART cycle beyond the
time of expected menses (i.e., 2 weeks after ovulation), is not proven
beneficial.
39.
40.
41.
42. Etiology of luteal phase defect
• Oocyte retrieval?
• Removal of granulosa cells
• hCG?
• Suppressing LH
• GnRH agonist? GnRH antagonist?
• Combination of these factors?
46. Cocherane 2011- Intervention review of different progesterone
regimens
• Comparison has 32 studies included with 9,839
women participants
• Investigated difference between different
progesterone regimens:
• Intramuscular (IM) versus oral
• IM versus vaginal or rectal administration
• Vaginal or rectal versus oral administration
• Low dose vaginal versus high dose vaginal progesterone
• Short protocol versus long protocol regimen
• Micronized progesterone versus oral progesterone
Van der Linden et al. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD009154.
47. Intervention result Comments
HCG vs Placebo No effect
P4 vs Placebo Beneficial 1.02 – 8.56 ( OR)
P4 Vs Hcg Same OHSS high
P4 Vs P4 +E2 Same
P4 Vs P4 + GnRh a Benefit 1.03 -1.67
48. Cochrae-2011: Micronized vaginal versus Dydroprogesterone
• Four studies with 698 events in 2388 participants reported
• A significantly better outcome of pregnancy is seen with
dydrogesterone
• Outcome: Pregnancy outcome rates
Van der Linden et al. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD009154.
Treatment A- Micronized Treatment B – synthetic
49. Dydrogesterone in LPS
• 2011, Cochrane Review showed a significant effect in favour of
progesterone for luteal phase support, favouring synthetic progesterone
over micronized progesterone.
• Dydrogesterone, is an oral progestin with improved bioavailability
compared with oral micronized progesterone.1
• In one randomized, controlled trial, pregnancy rates were higher in
women undergoing IVF using oral dydrogesterone for luteal support
versus vaginal micronized progesterone (41.0 vs 29.4%,P≤.01).2
Steroids. 2003; 68(10–13):927–9. ;Gynecol Endocrinol. 2007; 23(Suppl 1):68–72.
50.
51. Dydrogesterone in LPS
Conclusions: Oral dydrogesterone seems to be as effective as vaginal progesterone
for LPS in ART cycles, and appears to be better tolerated
52. Lotus I and Lotus II study
• Lotus I and Lotus II
demonstrate that oral
dydrogesterone is as
efficacious as MVP
(capsules or gel) for
luteal phase support in
fresh-cycle IVF, with a
similar safety profile
Dydrogesterone has the potential to induce a paradigm
shift for luteal phase support in the estimated 1.5
million women undergoing IVF each year
Gynecological Endocrinology. 2016 Feb 1;32(2):97-106.
53.
54. Dydrogesterone in LPS
CONCLUSION:
Since the outcomes of dydrogesterone are comparable to those of intramuscular
and vaginal progesterone, it is a reasonable option to provide luteal phase support
for women who are uncomfortable with injections or vaginal insertions.
55. Despite oral administration and first pass through the liver,
dydrogesterone was well tolerated and may become the new
standard for LPS in fresh embryo transfer IVF cycles
56. Advantages of Dydrogesterone over oral progesterone for LPS
1.Pandya M, Gopeenathan P, Gopinath et al. Evaluating the clinical efficacy and safety of progestogens in the management of threatened and recurrent miscarriage in early pregnancy- A review of the literature. Indian Journal of Obstetrics
and Gynecology Research. 2016;3(2):157–66.
2.Data on file for dydroboon.
Dydrogesterone
• Bioavailability is 5.6 times better
than oral micronized
progesterone1
• Receptor affinity is 1.5 times better
than oral micronized
progesterone1
• Low doses are required due to its
high potency2
Oral micronized progesterone
• Low bioavailability is attributed to its
significant first-pass effect1
• Less receptor affinity1
• High doses are required resulting in
side effects, such as drowsiness,
nausea, and headaches1
57. Advantages of Dydrogesterone from patients’ perspective
1. Griesinger G, Blockeel C, Tournaye H. Oral Dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril. 2018 May;109(5):756-762. 2. Salehpour S, Tamimi M, Saharkhiz N. Comparison of oral
Dydrogesterone with suppository vaginal progesterone for luteal-phase support in in vitro fertilization (IVF): A randomized clinical trial. Iran J Reprod Med. 2013 Nov;11(11):913-8.
01
Preferred route
by majority
patients
02
Higher patient
satisfaction
03
Easiest and
most acceptable
route of
administration
04
Stable form
05
Effective
06
Better
tolerability
07
Low side
effects/ good
safety profile
08
Excellent
patient
compliance
09
No androgenic
effects on fetus/
no side effects
for mother
58. Summary
LPS, Luteal phase support; IVF, In vitro fertilization; IUI, Intrauterine insemination
Progesterone is
essential for
establishing and
maintaining early
pregnancy
Absence of
exogenous
hormonal support
for LPS after IVF
is associated with
significant
reduction in
success rate
Progesterone is
critical to support
the luteal phase
following IVF and
widely used in IUI
cycles
Dydrogesterone,
an active
metabolite of
progesterone has
a good
bioavailability
Several trials have
demonstrated the
efficacy of
Dydrogesterone in
IVF and IUI