This document discusses strategies for optimizing ovarian response in ART to maximize live birth rates. It introduces the POSEIDON criteria for stratifying "low prognosis" ART patients based on age, ovarian reserve markers, and number of oocytes retrieved. The target is to retrieve over 15 oocytes to maximize cumulative live birth rates. Personalized gonadotropin protocols and adjuvant therapies can be used to optimize response based on POSEIDON stratification. This includes starting dose, supplementation with LH, and dual stimulation if needed to obtain the estimated number of oocytes for at least one euploid embryo transfer.
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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
Individualizing Ovarian Stimulation Protocols for IVFSherInstitute
Have you experienced poor response to IVF medications? Been told you had "Empty Follicle Syndrome?" Had lots of eggs retrieved but very few fertilized? Experienced Ovarian Hyperstimulation Syndrome? All of these issues can be tied to or affected by your protocol of stimulation. Dr. Geoffrey Sher presents his approach to customizing ovarian stimulation based on 30 years' experience in the IVF field. He outlines a number of his stimulation protocols and discusses the factors that can cause IVF failure due to improper stimulation protocols.
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.
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
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
Optimization of ovarian stimulation to improve success rate in ‘ART’Apollo Hospitals
ART is defined as the technique used where there is a need for in-vitro preparation or manipulation of gametes. The commonest ARTs are intrauterine insemination (IUI) and in-vitro fertilization (IVF). Ovarian stimulation is required with these procedures to increase the pregnancy rate as ART with natural cycle has a very low pregnancy rate. Optimizing pregnancy rates per cycle is the real basis for ovarian stimulation protocols in ART.
Individualizing Ovarian Stimulation Protocols for IVFSherInstitute
Have you experienced poor response to IVF medications? Been told you had "Empty Follicle Syndrome?" Had lots of eggs retrieved but very few fertilized? Experienced Ovarian Hyperstimulation Syndrome? All of these issues can be tied to or affected by your protocol of stimulation. Dr. Geoffrey Sher presents his approach to customizing ovarian stimulation based on 30 years' experience in the IVF field. He outlines a number of his stimulation protocols and discusses the factors that can cause IVF failure due to improper stimulation protocols.
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.
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
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
Optimization of ovarian stimulation to improve success rate in ‘ART’Apollo Hospitals
ART is defined as the technique used where there is a need for in-vitro preparation or manipulation of gametes. The commonest ARTs are intrauterine insemination (IUI) and in-vitro fertilization (IVF). Ovarian stimulation is required with these procedures to increase the pregnancy rate as ART with natural cycle has a very low pregnancy rate. Optimizing pregnancy rates per cycle is the real basis for ovarian stimulation protocols in ART.
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
Study design: A Randomized prospective comparable study.
Objective: To compare the effi cacy of GnRH agonist stop antagonist and GnRH antagonist protocols in ICSI outcome for women
who are expected to have poor ovarian response.
Setting: ART unit of Obstetrics and Gynecology Department of Qena University Hospital, South Valley University, Egypt.
Duration: From September 2016 to December 2017.
Improving Success by Tailoring Infertility Treatments - We are all individualsSandro Esteves
Aula ministrada pelo Dr. Sandro Esteves no 5th. Dubai International Obs-Gyne & Fertility Conference & eXHIBITION DIOFCE 2010, em 05 de novembro de 2010.
Air quality: is it that important? And if so, how to measure and control it?Sandro Esteves
Quality and Risk Management in the IVF Laboratory; Redlara Brasil, Belo Horizonte, 14-15 September 2016
Content:
1.Air quality: is it that important?
2. How to control?
3. How to measure?
Novel concepts in male factor infertility: clinical and laboratory perspectivesSandro Esteves
Presentation Objectives:
1. Update on the WHO reference values for semen parameters, and understand the role of sperm DNA fragmentation testing to decision-making strategies;
2. Learn how to counsel azoospermic men seeking fertility, and the role of gonadotropin therapy in this infertility condition;
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4. Appraise the role of medical and surgical interventions to infertile men undergoing ART.
Public lecture - Stem Cell and Male InfertilitySandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Public Lecture - Stem Cell and Male Infertility
Clinical management of men with nonobstructive azoospermia - Role of IVF Labo...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 5: Role of IVF Laboratory in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Sperm Retrieval ...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 4: Sperm Retrieval Methods in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Steps Before Spe...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 3: Steps Before Sperm Retrieval in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Chances of Harve...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 2: Chances of Harvesting Sperm in Nonobstructive Azoospermia
Clinical management of men with nonobstructive azoospermia - Azoospermia Diff...Sandro Esteves
Reproductive Andrology Workshop III
17-21 January 2016 - Kuwait City - KUWAIT
Organized by: Al Jahra Reproductive Medicine Unit - Ministry of Health
Lecture 1: Azoospermia Differential Diagnosis
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
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Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
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Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
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Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
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ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
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VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
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Optimize oocyte yield to maximize live birth in ART
1. Sandro C. Esteves
ANDROFERT & University of Campinas (UNICAMP),
Campinas, Brazil
Optimize oocyte yield to
maximize live birth in ART
2. 2 Modified from 1. Smith et al. JAMA 2015
156,947 UK women
(257,398 IVF cycles;
cumulative LBR using
fresh and frozen ET)
With increased women’s age in ART programs,
we should maximize reproductive outcomes and shorten TTLB
3. 3
Quality Dimensions
1. Effectiveness (Technical aspects to deliver the best outcome)
2. Safety (risks, adverse effects, lab quality, etc.)
3. Patient centeredness (patient values and preferences)
Success in ART
The bottom line
• Evaluate properly
• Give a fair estimate of outcome
• Develop a time-limited treatment plan
2. Dancet et al. Hum Reprod 2011; 3. Mainz. Int J Qual Health Care 2003
4. 4
AMH and AFC predict ovarian response but not LBR
AMH~AFC>FSH>Age
Predictors of Poor
Response
Predictors of Excessive
Response
Accuracy for Non-Pregnancy
Prediction ~ 50-55%
Modified from 4. Broer et al. Fertil Steril 2009 Modified from 4. Broer et al. Fertil Steril 2009Modified from 5. Broer et al. Hum Reprod Update 2011
Accuracy ~0.82 Accuracy ~0.78
5. 5
Only female age and number of oocytes can predict LBR
Modified from 6. McLernon et al. BMJ 2016
Modified from 7. Sunkara et al. Hum Reprod 2011
Modified from 8. De Geyter et al. Swiss Med Wkly 2015
7. 7
Low prognosis groups
Young Older
Adequate
ovarian
reserve
Poor
ovarian
reserve
Courtesy of Chloe Xilinas, EXCEMED
9. Poseidon Group. Fertil Steril 2016; 10. Humaidan et al. F1000Research 2016
8. 8 Modified from 11. Drakopoulos et al. Hum Reprod 2016
Low Prognosis Owing to Decreased Number of Oocytes
and thus lower CLBR
Poseidon Patients
Age-adjusted CLBR strongly influenced by oocyte number
* Age adjusted (OR: 0.9; 95% Cl: 0.9-1.01)
21.7%
39.7%
50.5%
61.5%p=0.002
p=0.02
p=0.01
9. 9 Courtesy of Chloe Xilinas, EXCEMED
Prevalence of low prognosis patients according
to POSEIDON criteria
5% 30%
10% 55%
47%
Poseidon
1-4
53%
Non Poseidon
N=432 – YEAR 2017
Source: ANDROFERT
10. 10
12. Esteves et al., Panminerva medica 2018
The older the women the lower the probability of euploid
embryos, thus increasing the risk of NO transferable embryos
Euploidy probability vs Female age Cycles with no transferable embryos
Courtesy of Chloe Xilinas, EXCEMED Courtesy of Ubaldi & Rienzi. Genera Jan 2012 – Dec 2013
11. 11 Esteves et al., ESHRE 2018; O-007; 12. Esteves et al. Panminerva Med 2019
Decline in blastocyst euploidy probability increases
progressively with female age
Analysis of 1,220 trophectoderm biopsies from 436 patients undergoing
ICSI and PGT-A with NGS
1.2 1.9 2.6 3.4 4.4
5.5
6.7
8.2
9.8
11.6
13.6
15.7
17.9
20.2
22.4
24.5
26.6
12. 12. Esteves et al. Panminerva Medica, 2019
To increase LBR/CLBR we need to maximize
the number of oocytes
% women with at least one euploid blastocyst as a function of age
and embryo cohort size
Embryo cohort
size: P<0.001
13. 13
Group 1
Young & Suboptimal/Low
Oocyte Number
Group 2
Old & Suboptimal/Low
Oocyte Number
Group 3
Young & Expected Low
Oocyte Number
Group 4
Old & Expected Low
Oocyte Number
High
embryo
aneuploidy
risk
Low
embryo
aneuploidy
risk
Few embryos generated
Reduced Cumulative Live Birth Rate
Poseidon
Patients
14. 14
The target is > 15 oocytes for maximizing CLBR
Courtesy of Chloe Xilinas, EXCEMED Modified from 11. Drakopoulos et al. Hum Reprod 2016
15. Introduced an Intermediate Marker of Success in ART:
the Ability to Retrieve the Number of Oocytes Needed to Obtain
at Least One Euploid Blastocyst for Transfer in Each Patient
15 9. Poseidon Group. Fertil Steril 2016; 10. Humaidan et al. F1000Research 2016
What is new in POSEIDON?
Introduced the Concept of ‘Low Prognosis’ in ART
Combined Oocyte Quality and Quantity for Identification
and Stratification of the ’Low Prognosis’ Patient
Included ’Hypo-responders’ as a Distinct Category
of ’Low Prognosis’ Patients
Introduced an Intermediate Marker of Success in ART:
the Ability to Retrieve the Number of Oocytes Needed to Obtain
at Least One Euploid Blastocyst for Transfer in Each Patient
16. 16
Estimation can be done by means of a mathematical function
taking into account relevant predictive factors
Input variables
• Maturation rate
• 2PN Fertilization rate
• Cleavage or Blastulation rate
• Euploidy rate per age group
Adjusted according to relevant
factors affecting fertilization rates
and embryonic parameters (eg.,
type of sperm, etc.)
Output variable
Y (N oocytes)
Function
Y = f(X)
19. 13. Esteves et al. Front Endocrinol 201919
Development of ART Calculator
Clinical & embryonic data of infertile
couples subjected to IVF/ICSI and
PGT-A (NGS)
26 co-variates analyzed
• Demographics
• Treatment characteristics
LASSO method for variable selection
• Female age, type of sperm used for
ICSI, and MII oocytes (p<0.0001)
Development predictive model using
logistic regression analysis
Internal validation by holdout method
20. 20
The easy way
13. Esteves et a. Front Endocrinol 2019
http://www.members.groupposeidon.com/Calculator
21. 21
The most optimal treatment strategy is planned with the
mindset to achieve the POSEIDON marker of success
GnRH analogue regimen
Gonadotropin dose and drug type
Trigger strategy
Adjuvant therapy
Combined strategies (AccuVit; Duostim, etc.)
Personalized use of laboratory technology
Personalized luteal phase support
22. 22 9. Poseidon Group. Fertil Steril 2016; 10. Humaidan et al. F1000Research 2016; 14. Haahr et al. Reprod Biol Endocrinol 2018
Gonadotropin starting dose and regimen can be determined
successfully in all patient categories by Poseidon-based stratification
(Ovarian biomarkers, Age, Number of oocytes if previous cycle)
Ovarian
Markers
Abnormal
Adequate
Age
G3 G4
G1 G2Suboptimal/
low oocyte
number
previous cycle Non POSEIDON SUB/LOW
YES
NO
23. 23
When exogenous gonadotrophin is administered,
the number of mature follicles recruited largely depends upon
the number of follicles attaining FSH sensitivity
The efficiency
of a stimulation protocol
must be measured by the effect
of gonadotropins at the ovarian axis,
and the quality of oocytes produced
24. 24
Modified from 17. Lehert P et al. Reprod Biol Endocrinol 2010
Oocyte yield per gonadotropin type
recFSH > uFSH, HMG and HP-HMG
1.5 oocytes (GnRH antagonist protocol)(18)
2.1 oocytes (16 RCT; different protocols)(17)
3.1 oocytes (GnRH antagonist)(19)
2.8 oocytes (GnRH agonist protocol)(20)
1.8 oocytes (GnRH agonist protocol)(21)
17. Lehert P et al. Reprod Biol Endocrinol 2010; 18. Devroey et al. Fertil Steril 2012; 19. Bosch et al. Hum Reprod 2008;
20. Hompes et al. Fertil Steril 2008; 21. Andersen et al. Hum Reprod 2006
25. 25 Esteves, Yarali, Ubaldi et al. ESHRE 2019; submitted
No detrimental effects on embryo ploidy in patients
who retrieve more oocytes
Response Number Euploid Blastocysts
Distribution Binomial
Estimation Method Logistic Regression
Validation Method Validation Column
Probability Model Link Logit
Generalized Regression for number
Euploid Blastocysts Model Launch
Lasso [x] Adaptive
Term Estimate Std Error
Wald
ChiSquare
Prob >
ChiSquare
Lower
95%
Upper
95%
Intercept 6.2769104 0.6256681 100.64771 <0.0001* 5.0506235 7.5031972
Age Female -0.182507 0.152275 143.64894 <0.0001* -0.212352 -0.152662
Number
Blastocysts
0.0302516 0.0189943 2.536584 0.1112 -0.006977 0.0674797
Parameter Estimates for Original Predictors
3,108 Trophectoderm Biopsies
1,109 patients
Euploidy probability vs. number
of blastocysts by age group
26. 26
Higher ovarian response than that achieved with mild/natural
ovarian stimulation does not increase risk of embryo aneuploidy
Term Estimate Std Error
Wald
ChiSquare
Prob >
ChiSquare
Lower
95%
Upper
95%
Intercept 3.8117137 1.5331832 6.1809102 0.0129* 0.8067298 6.8166876
Age Female -0.22129 0.019748 125.56789 <0.001* -0.259996 -0.182585
typeOSGrou
ped[Convent
ional-Other]
0.065727 0.33909 0.0375714 0.8463 -0.598877 0.7303311
Response Number Euploid Blastocysts
Distribution Binomial
Estimation Method Adaptive Lasso
Validation Method Validation Column
Probability Model Link Logit
Adaptive Lasso with Validation Column Model Summary
Parameter Estimates for Original Predictors
1,632 Trophectoderm Biopsies by NGS
631 patients
Euploidy probability vs Female Age, by OS Type
Esteves, Yarali, Ubaldi et al. ESHRE 2019; submitted
27. 27
Administration of an inappropriately low gonadotrophin dose
may lead to the growth of a low number of follicles resulting
in an ‘iatrogenic’ poor or suboptimal response
• Type of Gonadotropin
• FSH Dose
• Add LH
Courtesy of Chloe Xilinas, EXCEMED
Follicle-to-Oocyte Index (FOI)
(No. retrieved oocytes/AFC)x100
15. Alviggi, Conforti, Esteves et al. Front Endocrinol 2018
28. 28
Agonist or Antagonist rFSH alone
or rFSH + rLH (2:1 ratio)
Agonist or Antagonist rFSH
+ rLH (2:1 ratio)
GnRH Antagonist + Low dose rFSH (100-175 IU) GnRH Antagonist + rFSH + rLH (150:75 IU)
Poseidon
G1 Poseidon
G2 Poseidon
G3 Poseidon
G4
Non
Poseidon
patients
22. Andersen et al. (eds.) Research Topic Frontiers in Endocrinology. In preparation
It is important to use the right gonadotropin regimen and adapt it
during the cycles to optimize the number of oocytes retrieved and at
the same time minimize risks such as OHSS and cycle cancellation
29. 29 Unpublished data; Source: ANDROFERT
Current Practice – Flexibility of iCOS
Rec-hFSH
Starting Dose Distribution (%)
% cycles with
Dose Adaptation after Sd5
53.4%
30. 30
Current Practice – Flexibility of iCOS
% cycles
by Trigger Method
% cycles
with LH Activity Supplementation
12%
Dual trigger
43%
GnRH analog
45%
hCG
57%
Rec-LHc
43%
No-LH
Unpublished data; Source: ANDROFERT
31. 16. Conforti, Esteves, Cimadomo et al. Front Endocrinol (under review)31
PHARMACOLOGICAL INTERVENTION
32. 1)Patients with sufficient prestimulation
ovarian reserve parameters that have an
unexpected hyporesponse to FSH
monotherapy
r-hLH can be started either during the
midfollicular phase to rescue the ongoing cycle
or on stimulation day 1 in a subsequent cycle
2) Women 36–39 years
r-hLH should be started on stimulation day 1
23. Alviggi et al. Fertil Steril 2018
33. 33
Target number of oocytes difficult to achieve by a single OS cycle
13. Esteves et al. Front Endocrinol 2019
Courtesy of Chloe Xilimas, EXCEMED
http://www.members.groupposeidon.com/Calculator
Thank you for the introduction, Mr. Chairperson.
Ladies and gentlemen, colleagues and friends, good morning.
A problem we face nowadays is that the proportion of patients with advanced age is increasing steadily in our clinics.
We all know that pregnancy rates are lower in these women than in their younger counterparts.
However, we should also realize that the repetition of IVF treatments using a trial and error approach does not seem to help these patients much because the gap between young and older patients concerning cumulative live birth actually increases after multiple IVF cycles.
In the era or personalized medicine, Success in IVF goes far beyond pregnancy.
It should be redefined using other quality dimensions, without overlooking the patient perspective.
My personal approach includes the provision of proper evaluation, counseling about the chances of success, and development of a time-limited treatment plan taking in full consideration what the patient values and preferences are.
Most of us now use ovarian biomarkers, like AMH and AFC, to predict ovarian response to gonadotropin stimulation.
Despite their unquestionable clinical value in that regard, we should not use their results to counsel our patients about their chances of success in IVF.
What became clear though over the last years is that if we want to maximize live births we should optimize oocytes yield.
However, oocyte number should be used in combination with female age since the likelihood of delivering a baby among patients with similar oocytes yield ultimately depends on female age.
This means that the number of oocytes needed to maximize live births should be individualized taking into account female age, and more importantly, patient-oriented strategies can be used to achieve the individualized oocyte number.
These aspects make the foundations, ladies and gentlemen, of the novel POSEIDON criteria that you might have heard about.
The POSEIDON criteria propose a shift from the current terminology of POR to the concept of low prognosis.
The low prognosis patients are classified into four groups based on female age, results of ovarian biomarkers, and the number of oocytes retrieved in previous cycle if that information is available.
You may want to know why POSEIDON patients have low prognosis in IVF.
The answer is very simple.
Patients fitting into the POSEIDON criteria have low prognosis owing to a decreased number of oocytes, a situation that can be further aggravated by ageing and will affect cumulative live birth rates.
I feel we should care about the new POSEIDON criteria because a significant proportion we treat in our Clinics will fit in one of the POSEIDON categories.
In POSEIDON, based on female age, patients are classified as groups 1 and 2 if younger than 35 years, and as groups 2 and 4 if older than that.
Female age is a critical element because it is related to embryo ploidy.
In a study by the POSEIDON group we are presenting in this meeting, we calculated the probability of a blastocyst being euploid as a function of female age.
This probability sharply declines after the age of 34, and is lower than 50% overall in older patients.
This phenomenon, in combination with the already reduced ovarian reserve in older patients, leads to an increased risk of having no euploid embryos for transfer in such patients.
This issue gets more and more complicated as the patient ages.
In this study -also by the POSEIDON group- we presented this morning, we found that the % decrease in blastocyst euploidy probability progresses with every year of age.
In young patients the loss is low from one year to the next year; however, it increases remarkably as the patient ages.
Overall, POSEIDON patients can be summarized like this:
In groups 1 and 3 patients are young, and therefore the risk of embryo aneuploidy is relatively low.
By contrast, in groups 2 and 4 patients are older, thus increasing the risk of embryo aneuploidy.
The bottom line is that in all categories, the number of embryos generated is likely to be low, thus affecting the cumulative live birth rate.
You may have now realized that the prognosis of POSEIDON patients differs according to the group category.
Big data indicates that the number of oocytes to maximize cumulative live births should be higher than 15.
Although this number gives us general guidance, it might be hard to achieve in POSEIDON patients.
I feel we can do better than this by determining the individualized oocyte number for each patient we treat.
In this regard, besides the classification system, the POSEIDON initiative gives us a hand, as it introduced an intermediate marker of success in ART, namely, the ability to retrieve the number of oocytes needed to obtain at least one euploid blastocyst for transfer in each patient.
We feel this is a fair outcome to offer our patients, because transfer of a euploid embryo is associated, at any given age, with implantation rates in the range of 50-60%.
The good news is we can estimate what that number is.
For this, we have to compute the results of variables more likely to affect the number of resulting embryos and their genetic competence.
One option would be for you to look into your database and find out the results of relevant variables and then make the calculations.
Another option is to use the ART Calculator, a prediction model we developed to make these calculations easy for busy doctors like us.
The study aimed at developing a calculator to predict the POSEIDON marker of success.
We analyzed clinical and embryonic data of infertile couples who underwent IVF/ICSI with PGT-A.
We used the LASSO method for variable selection. The fitted model selected female age, type of sperm used for ICSI, and MII oocytes as predictors.
Final predictive model developed using logistic regression analysis, and internally validated by the holdout method.
Predictive ability of the model evaluated by the ROC curve (AUC=0.72)
The model generates the individualized probability of blastocyst euploidy per MII oocyte, and using mathematic equations provides the minimum number of MII oocytes required for >=1 euploid blastocyst, with 95% CI interval.
A calculator was then developed to make 2 types of prediction automatically, one pre-treatment and another post-treatment.
In this movie, you can see how the calculator works,
Pre-treatment, all you have to do is provide the patient age, and the type of sperm used for IVF/ICSI.
Then, with a single click, the calculator provides an estimation of the number of MII oocytes needed to obtain at least one euploid blastocyst.
In case the number of mature oocytes, as initially predicted, is not achieved, the calculator estimates the chances of having a euploid blastocyst using the number of MII oocytes retrieved.
The ART Calculator may assist in clinical counseling and individualized treatment planning.
We feel that the POSEIDON patient stratification and the estimation of the number of oocytes needed to obtain at least one euploid blastocyst for transfer are a perfect match.
This combination can guide clinicians to select the most optimal treatment strategy with the mindset to achieve the POSEIDON marker of success, with the ultimate goal of reducing the time to live birth.
In practical terms, the individualized oocyte number can be achieved using patient-oriented strategies.
For instance, gonadotropin starting dose and regimen can be tailored according to the POSEIDON stratification.
A crucial decision-making aspect regarding gonadotropin choice is that the number of competent follicles at the end of stimulation depends on the number of follicles attaining FSH sensitivity.
In this regard, overwhelming evidence indicates that oocyte number is optimized by use of recombinant FSH.
Importantly, patient-oriented gonadotropin doses aimed at retrieving more oocytes do not affect embryo genetic competence.
In this ongoing study by the POSEIDON group, the age-controlled probability of a blastocyst being euploid is not affected by the size of the embryo cohort, thus confirming previous observations of no detrimental effect on embryo euploidy in patients who retrieve more oocytes.
Our observations also indicate that use of mild or minimal stimulation as a means of improving embryo genetic competence is unsound.
What matters concerning embryo ploidy is female age and not the intensity of ovarian stimulation.
On the contrary, use of low gonadotropin dose might result in hypo-response and retrieval of fewer than expected oocyte number.
This phenomenon is clearly seen in POSEIDON groups 1 and 2 patients, who despite adequate prestimulation parameters end up having poor or suboptimal oocytes yield, possibly due to use of inappropriate low gonadotropin dose or presence of polymorphisms affecting gonadotropins and their receptors.
As I said before, and highlight here again, proper patient evaluation is key not only to identify the low prognosis patients,
But also plan a treatment tailored for the patients specific needs.
Naturally, use of right gonadotropin starting dose, and the possibility to adapt the dose during the cycle is essential to optimize oocytes yield while securing patient’s safety.
In our practice, we routinely use iCOS.
Different gonadotropin starting doses are chosen and adapted during the cycle –whenever needed- to increase the chances of achieving the individualized oocyte number and at the same time minimize risks such as OHSS and cycle cancellation.
We apply the same reasoning concerning LH supplementation, trigger methods and luteal phase support.
For instance, both non-Poseidon patients and those fitting in Poseidon groups 1 & 2 greatly benefit from pharmacological interventions as a means to increase oocyte yield and minimize risks, including OHSS and suboptimal response.
This includes the use of not only the right FSH starting dose but also evidence-based recombinant LH supplementation, which is particularly beneficial to Poseidon’s groups 1 and 2 as well as women aged 36-39 treated with the antagonist protocol.
However, even using the best protocol it might be hard to achieve the optimal individualized oocyte number in single stimulation.
This is particularly true for patients of POSEIDON’s groups 3 and 4, who are the ones with abnormal ovarian markers.
Consecutive ovarian stimulation in the follicular and luteal phase, know as Duostim, is an attractive strategy to be considered in patients of POSEIDON’s groups 3 and 4.
The target number of oocytes might be reached quicker, thus increasing the likelihood of having at least one euploid blastocyst in the resulting embryo cohort.
Mr. Chairman, ladies and gentlemen, I now come to the end of my presentation.
I strongly believe that the use of POSEIDON-based stratification along with iCOS, with the mindset to achieve the individualized oocyte number, is the way to reduce the time to live birth.
We started using this system over a year ago, and we are delighted with the results.
It gives us guidance on how to most optimally treat each patient.
Using the POSEIDON criteria and the ART Calculator, we are also able to provide transparent information, which helps our patients prepare both emotionally and financially for the treatment journey.
I like to call this model “Individualized Assisted Reproductive Technology”
I invite all of you to know more about the POSEIDON initiative and the ART Calculator.
I also encourage you to join us and become a member of the POSEIDON group.
Thank you very much.