It describes the Progesterone physiology. It describes the latest evidence as regards progesterone formulations, use of progesterone as Luteal phase support. It scrutinizes the value of serum progesterone in monitoring luteal phase
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 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.
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 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.
Role of Dydrogesterone in Threatened Abortion Dr Sharda Jain Lifecare Centre
*EXPERINCE SHARING By EXPERTS*
Dr Uma Rai(DGF *E*)
Dr Sangeetaa Gupta(DGF *E*)
Dr Neerja Varshney(DGF *E*)
Dr Surjeet Kapoor(DGF *E*)
Dr Rupam arora(DGF *E*)
Dr Meenakshi Ahuja(DGF *S* )
Dr.Harsha khullar(DGF *C* )
Dr Mamta mittal(DGF *N*)
Dr Leena Sreedhar(DGF *D*)
Dr.Dipti Nabh(DGF *E*)
Dr. Shama Batra(DGF *E*)
Dr Poonam Paul(DGF *SW*)
PAN DGF ( DELHI GYNAECOLOGIST FORUM) CME ON DYDROGESTERONE ON 3/2 /22
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
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
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
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
Miscarriage is pregnancy loss before 22 weeks’ gestation based on the LMP or if gestation age is unknown, it is the loss of an embryo or a fetus of less than 500g.
Role of Dydrogesterone in Threatened Abortion Dr Sharda Jain Lifecare Centre
*EXPERINCE SHARING By EXPERTS*
Dr Uma Rai(DGF *E*)
Dr Sangeetaa Gupta(DGF *E*)
Dr Neerja Varshney(DGF *E*)
Dr Surjeet Kapoor(DGF *E*)
Dr Rupam arora(DGF *E*)
Dr Meenakshi Ahuja(DGF *S* )
Dr.Harsha khullar(DGF *C* )
Dr Mamta mittal(DGF *N*)
Dr Leena Sreedhar(DGF *D*)
Dr.Dipti Nabh(DGF *E*)
Dr. Shama Batra(DGF *E*)
Dr Poonam Paul(DGF *SW*)
PAN DGF ( DELHI GYNAECOLOGIST FORUM) CME ON DYDROGESTERONE ON 3/2 /22
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
Invited Lecture delivered by Dr Sujoy Dasgupta in the Annual Conference of ISAR (Indian Society of Assisted Reproduction) held at Kolkata in November, 2019
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
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
Miscarriage is pregnancy loss before 22 weeks’ gestation based on the LMP or if gestation age is unknown, it is the loss of an embryo or a fetus of less than 500g.
The thin endometrium refers to the lining of the uterus, known as the endometrium, being insufficiently thick. This condition is typically characterized by a reduced thickness of the endometrial layer, which plays a crucial role in supporting the implantation and development of a fertilized egg during the menstrual cycle.
A thin endometrium is commonly associated with hormonal imbalances, such as low estrogen levels, which are vital for the growth and maintenance of the endometrial tissue. Inadequate blood flow to the uterus, chronic inflammation, or certain medical conditions can also contribute to this condition. Women with a thin endometrium may experience difficulties in achieving and maintaining pregnancy, as the thin lining may not provide an optimal environment for the embryo to implant and thrive.
Addressing the underlying causes of a thin endometrium often involves hormonal therapies to regulate estrogen levels, lifestyle modifications, and sometimes surgical interventions. Fertility treatments, such as in vitro fertilization (IVF), may be considered to overcome the challenges associated with a thin endometrium.
In conclusion, a thin endometrium can pose challenges to fertility and reproductive health, requiring a comprehensive approach to address the underlying factors and improve the chances of successful conception.
This presentation discusses the basics and updates about the assessment and management of chronic pelvic female in women. It highlights the recent thoughts about the biopsychosocial model of chronic pelvic pain. It provides an algorithm that joins the management between primary and tertiary care in the management of CPP.
this presentation highlights the principles of uterine and ovarian transplantation. It explores the past and examines the current status for uterine and ovarian factor infertility.
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.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
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.
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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
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
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
4. To review the major concepts and display the updates as regards:
1- Luteal phase physiology.
2- Progesterone as a hormone.
3- Different Progesterone preparations.
4- Serum Progesterone and ART.
5- Luteal phase management with the use of Progesterone as a luteal
phase support.
6- Pharmacological use of Progesterone during early pregnancy
5. • Multiple uses of progesterone and progestogens for women’s health
in clinical practice are recognized.
• Its use is of good- quality evidence for some indications
• Preterm labor prevention.
• Balance estrogens in hormonal replacement therapies
• For oral contraception
• Palliative care for the treatment of gynecological malignancies.
• On the other hand, the role of progesterone for luteal phase support
still represents a controversial topic, due to its wide and empirically
transverse clinical use, from natural ovulatory cycles to (ART).
7. Progestogens are hormones that bind to
the progesterone receptors.
During the midluteal phase, ovarian P4
production increases up to 25–50 mg/day.
23
members
8. Timeline of development
• 1934: isolated from animal CL.
• 1941: synthesized from plant sterol.
ButPoor gut absorption. Micronisation ButPoor bioavailability 5%.
• 1960s: Dydrogesterone (retroprogesterone) by UV exposure of the
progesterone: 28% bioavailability.
9. Synthesis of progesterone
Starts in response to
LH surge.
LH surge luteinizes
both granulosa and
theca cells.
Rapid increase in
serum of P4 and its
metabolite.
10. Role of progesterone in early pregnancy
• The physiologic effects are mediated by interaction
with progesterone receptor (PR).
• There are two classic PR isoforms: PR-A and PR-B.
• PR-A is required for normal ovarian and uterine function.
• PR-B is critical for mammary development.
13. I. Normal Luteal Phase
According to Speroff & Fritz:
(1) normal luteal phase lasts from 12 to 14 days.
(2) progesterone secretion occurs in pulses.
(3) peak of progesterone levels in non-pregnancy cycles occurs 6–8
days after ovulation.
(4) progesterone secretion after implantation is regulated by hCG.
14. Assessment of luteal phase
• Basal body temperature (BBT) evaluation: inconvenient and not
precise
• Urinary luteinizing hormone (LH) surge detection kits: unreliable.
• Serum progesterone levels.
• Endometrial biopsy.
• ERA test
Practice Committee of the ASRM [2015]: “there are no practical standards to
diagnose LPD. The above-described methods (BBT, urinary LH kits, serum P4 levels
and endometrial biopsy are not recommended to confirm LPD”.
15. Serum progesterone levels
Not accurate nor precise:
• It is difficult to know the onset of luteal phase (ovulation time) which
is important to diagnose progesterone peak.
• Progesterone is secreted in pulses as the response of LH pulses/ 90
minutes.
• Intra-cycle variation: During pulse, its level can be 6–8 times higher.
• Inter-cycle variation: The hormonal activity (progesterone secretion)
of corpus luteum is different in subsequent cycles.
16. Endometrial biopsy
• Theoretically, LPD is diagnosed when histologic characteristics is
delayed ≥2 days in relation to known day of luteal phase.
• However, 2 big trials have shown the imprecision to diagnose luteal
phase adequacy and the inability to discriminate between infertile
subjects and fertile controls.
17. “ERA test”
The endometrial window of implantation (WOI), the cycle days during which normal embryo
implantation can occur, has generally been assumed to begin on cycle day 19 or 20 of an idealized 28
days cycle and last for 4 to 5 days.
The endometrial receptivity array [ERA] test is a molecular diagnostic
biomarker tool that identifies the receptive endometrium in natural and artificial
(hormonal replacement therapy) cycles.
20. I. Types of progesterone supplementation
Selection of the most optimal
route of administration
should consider:
-Peak plasma concentrations.
-Possible side effects.
-Patient compliance.
Progesterone is administered
in 3 different ways:
-Oral.
-Vaginal.
-Intramuscular.
21. I- IM (Progesterone in oil)
Advantages
• Long lasting since 1980s
• Effectiveness.
• The gold standard.
Disadvantages
• Local side effects: pain/ swelling
and redness
• Painful nodules and aseptic
abscesses
• Severe cases of acute
eosinophilic pneumonia
22. II- SC progesterone
Advantages
• Subcutaneous (comfortable)
• 25 mg
• Safe
• Cmax values: 4-folds higher than
progesterone-in-oil IM
• Effective in supporting the luteal
phase in IVF patient.
• Non-inferior to Vaginal
Progesterone on the on-going
pregnancy rates at 10 weeks.
Disadvantages
• Rare: local reactions.
23. III. Oral route
Advantages
• Optimal compliance
Disadvantages
• Absorption can be affected by food,
rate of gastric emptying, GI motility,
GI secretions and increasing
splanchnic blood flow
• Hectic plasma concentration
(enterohepatic circulation and
variable gastric filling).
• Side effects: nausea & sleepiness
• Metabolites produced during passage
through the liver
24. Oral forms
Micronized progesterone
• In the late 1980s,
• Derived from plants.
• Micronization of progesterone in
particle sizes of < 10 um increases
the available surface area of the
drug and enhances the aqueous
dissolution rate and intestinal
absorption of progesterone.
• Not preferred now as oral route
Dydrogesterone
• Selective and strong receptor
affinity.
• High oral bioavailability.
• May have lower side effects.
• Active metabolites
• immunological beneficial effects
• Lotus I study
• Lotus II study
25. Dydrogesterone
Advantages
• Low dose
• Minimal side-effects
• Reduce the likelihood of altered
liver function.
Disadvantages
• Extensive first-pass metabolism
of oral progesterone limits its
efficacy
• May increase the risk of
intrahepatic cholestasis in
predisposed women
26. Lotus I: 05/ 2017
• RCT, double-blind, double-dummy,
Phase III
• For luteal phase support in fresh
cycle IVF.
• 1031 patients.
• Oral dydrogesterone (30 mg Vs
micronized vaginal progesterone
capsules (600 mg [200 mg three
times daily).
• Non-inferiority of dydrogesterone
to micronized vaginal progesterone
capsules was demonstrated (33.1%
Vs 37.6%)
Lotus II: 12/2018
• RCT, open-label, Phase III
• For luteal phase support in fresh
cycle IVF.
• 1034 patients
• Oral dydrogesterone (30 mg Vs 8%
micronized vaginal progesterone gel
(90 mg once daily).
• Non-inferiority of dydrogesterone
to micronized vaginal gel
27. IV. Vaginal Route
• Higher concentrations of the drug in the uterine tissue.
• First direct preferential vagina-to-uterus transport
• Treatment effects are significantly improved.
• Reducing the likelihood of undesirable side effects.
• Time-to-peak concentration tends to be slightly longer.
• After vaginal administration, plasma concentrations achieves
a plateau-like profile and are more constant in comparison to
oral delivery.
Passive diffusion through tissues.
Transluminal passage
Venous or lymphatic transfer.
Countercurrent vascular exchange.
28. Vaginal soft capsules of micronized
progesterone
Advantages
• Long lasting: 1990s.
• Compliance.
• Limited side-effects.
• Proper secretive transformation
of the endometrium.
• Provides greater bioavailability
of the active component at
endometrial level with lower
plasma progesterone levels.
Disadvantages
• Low doses were less effective than
IM route. However, the 600
mg/day yields comparable results
to IM.
• Vaginal leakage, which implies that
the real dosage adsorbed cannot
be assured.
• Local discomfort as genital itching,
genital irritation, vaginal discharge,
candidiasis, dyspareunia.
29. Endometrin vaginal tablets
Advantages
• FDA approval.
• Less vaginal irritation and
“messiness”
• Better adhesion and lesser
leakage.
Disadvantages
• Increased expense.
30. Vaginal progesterone bioadhesive gel
Advantages
• The same pharmacokinetic profile
as the capsule formulation.
• Comparable results to IM
progesterone in oil in preventing
spotting.
• Equivalent efficacy to all other
vaginal progesterone forms in
terms of clinical pregnancy rates in
ART
Disadvantages
• Expense
31. Progesterone releasing vaginal ring
• The progesterone vaginal ring is a device used for continuous release
of micronized progesterone; phase III trials are ongoing.
• This type of ring contains 1 g of natural progesterone and provides a
continuous and constant release of approximately 10 mg/day of
progesterone for at least 90 days.
• It can induce secretory transformation of endometrium after an
appropriate pretreatment with estrogens
32. Luteal phase support in ART with the
use of Progesterone
“Luteal Phase Medicine”
33. I. Value
•One of the agreed upon few points
is that progesterone during the
luteal phase increases the success
rate in ART (Higher rate of ongoing
pregnancy or live birth (OR 1.77).
34. II a. When to start ?_Fresh cycle
(i) after hCG
administration
for final oocyte
maturation
(ii) on the day
of oocyte
retrieval
(iii) on the
day of
embryo
transfer
Beginning of the luteal support 6 days after oocyte retrieval is associated with significantly lower
rates of clinical pregnancies because the exogenous progesterone deficit negatively impacts on
anatomical and functional changes of endometrium that characterize the “window of implantation.”
35. IIb. When to start ?_FET cycle
Pregnancy rate is similar when progesterone replacement
started at a time corresponding to the day of pick-up or the
day after pick-up, but worsened when the progesterone was
initiated at a time corresponding to the day before the pick-up
FET should be performed after a progesterone
replacement period equivalent to the embryo age
or to the embryo age plus 1 day. For example, if
the embryo was cryopreserved as a 3-day-old
embryo, the transfer should be scheduled after 3
or 4 days of progesterone administration.
36. III. When to stop?
• hCG secreted by the trophoblast
in progressively increasing
amounts from the beginning of
pregnancy, makes continuation of
exogenous progesterone
supplementation of limited value.
• An RCT found no differences in
terms of ongoing pregnancy,
deliveries or miscarriage rates
between the women (+hCG and 3
weeks)
37. IV. What dose?
Member
• IM progesterone
• SC progesterone
• Endometrin
• Crinone
• Micronized progesterone in capsules
• Dydrogesterone
Dose
50 mg/day
25 mg /day
200-300 mg/day
90-180 mg/day
300-600 mg/day
30 mg/day
The threshold of 10 ng/ml, which is close to the value reported as an
adequate progesterone production by the CL in natural cycles (Hull et al., 1982)
38. Serum Progesterone and ART.
I. Fresh Cycle: Late Follicular Elevated Progesterone
II. Frozen Cycle:
39. Luteal phase monitoring
Early luteal monitoring (OPU + 2)
• P4 levels exhibit a non-pulsatile
pattern in both the natural and
stimulated cycle (low values are
truely low)
• High accuracy of P4 assay.
• Detects a low prevalence of
patients in need of treatment
adjustments.
• A theoretical good chance to
correct for low P4 patients by use
of additional exogenous P4.
Mid-luteal monitoring (OPU + 7)
• Higher risk of P4 fluctuations in the
high P4 group of patients.
• Low accuracy of P4 assay
• Detects a higher proportion of
patients who require a change in
treatment.
• An intensified luteal phase support
to low P4 patients may be less
efficient late in the cycle.
To shift from the ‘one model fits all’ and towards a more individualized luteal phase support policy
40. Serum
P4
Fresh cycle
Basal P4
< 0.7
Late
Follicular
< 1.5
Early
Luteal
20-30
Mid-Luteal
45-80
As compared to Cleavage stage transfer, Blastocyst can
withstand transfer up to serum P4= 1.75 ng/dl
42. Fresh Cycle
Late Follicular Elevated Progesterone
• Defined as a serum P4 of ≥ 4.77 nmol/l (≥1.5 ng/l) on completion of COS,
before administration of HCG (Bosch et al., 2010; Venetis et al., 2015).
• The supraphysiologic milieu of hormones produced during ovarian
stimulation may affect endometrial receptivity (embryo–endometrial
asynchrony) and hinder both pregnancy rates and neonatal outcomes.
A meta-analysis of over 60 000 IVF cycles shows the presence of LFEP is associated with a significant
decrease in the probability of pregnancy, (Venetis et al., 2013).
• This may be due to:
• An abnormal endometrial gene expression (Labarta, et al., 2011, Van Vaerenbergh, et al., 2011).
• An atypical epigenetic profile in the luteal phase.
43. I. Risk factors of LFEP
Non-Modifiable Risk Factors
• Female age.
• Basal FSH.
• Basal Progesterone.
Modifiable Risk factors
• Duration of stimulation.
• Serum E2 on day of hCG.
• Number of oocyte retrieved.
• Number of 2 pronuclear oocytes.
44.
45. II. Diagnosis of LFEP
• Absolute Figure: > 1.5 ng/dL. In average or low responders. 1.75ng/dL
in high responders.
• Single P4 measurement: Not precise.
• P4-to-follicle (Shufaro, et al., 2015)
• P4-to-oocyte (Hill, et al., 2017)
• P4-to-estradiol (Younis, et al., 1998, Lai, et al., 2009, Wu, et al., 2012).
46. III. Basal serum P4 in LFEP
• Basal progesterone (ovarian or
adrenal origin) is exhibits an
independent association with the
occurrence of PE regardless of the
intensity of ovarian stimulation.
• The presence of a corpus luteum
that did not undergo functional
luteolysis
47. IV. How long is the LFEP?
• “For how long can we allow the
endometrium to be exposed to P
above a certain universal
threshold?”.
Cycles with an increasing duration of LFEP >1.50 ng/mL are associated
with a significant decrease in LBR. However, the relative frequency of
having such LFEP levels for >1 day was so rare (1.9%).
48. V. Predict and prevent the “LFEP”
• Identification of variables that could identify patients at risk for PE on
the day of hCG.
• Pretreatment with oral contraceptive pill or corticosteroids might
reduce the reoccurrence of high basal progesterone.
• Careful addition of LH activity during stimulation.
• Prevent the occurrence of PE: milder ovarian stimulation that results
in a lower number of oocytes.
49. VI. Manage the “LFEP”
• Counsel the patient.
• Freezing all embryos and deferring embryo transfer for a
subsequent frozen-thawed cycle Transfer.
51. Progesterone in miscarriage
threatened/ recurrent
Theoretical
• Improved endometrial blood flow.
• Immunological properties.
• Increase Nitric oxide synthesis in
human vascular endothelial cells in
vitro, mainly mediated through mPRα.
• Dydrogesterone (main metabolite
DHD) elicits a consistent increase in
nitric oxide synthesis from these cells.
PROMISE trial
• 836 patients with RM.
• Vaginal Progesterone 400 mg
vaginally from positive pregnancy
test to 12th week of gestation).
• No significant reduction in live
birth after 24 weeks of gestation,
neither miscarriage rate.
• The main limitation is the lack of
luteal supplementation
52. Conclusions
• Progesterone is essential for pregnancy initiation and maintenance.
• Different progesterone preparations exist allowing alternative choices
for each case.
• LFEP should be first prevented by soft ovarian stimulation protocols.
• Serum progesterone may have a role in standardizing ET protocols.
• Progesterone has little –if any- role in the management of threatened
and recurrent miscarriage.