Personalised medicine in reproduction€¦ · EBM . PTM . Multi-variate . prediction models ....
Transcript of Personalised medicine in reproduction€¦ · EBM . PTM . Multi-variate . prediction models ....
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Prof.Dr. Bart CJM Fauser
Personalised medicine in reproduction
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Disclosure of interest, Fauser
Professor of Reproductive Medicine Chair, WHO steering committee infertility guidelines Board member Dutch Medical Research Counsel Chief Editor Reproductive Biomedicine Online COGI chair Executive boards international organisations Consultant various pharmaceutical companies Visiting professor at different international institutions
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Personalised healthcare
Personalised medicine
The era of personalised medicine
Adapted from Pokorska-Bocci A, et al. Pers Med 2014;11:197–210
P4 medicine (Predictive, Preventive,
Personalised, Participatory)
Individualised medicine
Stratified medicine
Precision medicine
Targeting therapy Biomarkers and drugs
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Developments in clinical research
2016
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JAMA 2014
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Current evidence based medicine paradigm
Patie
nt p
opul
atio
n
A
B
EBM
95% CI difference
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2014
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2014
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Standard vs tailored approach in medicine
Herceptin, Breast cancer
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Paradigm shift from evidence based to patient tailored medicine (2) Pa
tient
pop
ulat
ion
Intervention
A
B
X
Primary Outcome
Standardized phenotyping
EBM
PTM
Multi-variate prediction models
hom
ogen
eous
he
tero
gene
ous
95% CI difference
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2015
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The EBM paradigm
Meta analysis
experimental
observational
IPD Meta analysis
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Examples of personalised care in infertility
Ongoing pregnancy chances in unexplained
infertility
Previous attempts to
individualise infertility care
have been based around:
Markers for ovarian reserve /
reponse to stimulation
CAT serum test association with tubal infertility
Live birth following ovulation induction
in PCOS
Prediction of pregnancy
complications & child outcomes in
PCOS
Markers for implantation failure
(gene expression, microbiome)
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Hunault model Habbema, Hum Reprod 2015 Hunault, Hum Reprod 2005 Hunault, F&S 2002 Eimers, F&S 1994 Collins, F&S 1989
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CC for ovulation induction in PCOS
Ovulation
Pregnancy (35-40%)
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Prediction Medicine, methodology
Prospective, cohort follow-up study Single or no (natural cause of disease) intervention Define primary (or composite) endpoint Univariate association analysis Multi-variate analysis (preferably no more than 10 variables) Development prediction model
External validation prediction model
JCEM 1998
AUC 0.84
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CC ovulation induction in WHO 2 - outcome prediction
Nomogram; live birth (age, BMI, cycle, FAI)
Imani, JCEM 1998 Imani, JCEM 1999 Imani, JCEM 2000 Imani, F&S 2001
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n=626 RCT; CC, Metformin, or both up to 6 cycles Basline characteristics and prediction of ; ovulation, conception, pregnancy, live birth FAI, BMI, Proinsulin, duration attempting conception
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Ovarian stimulation for IVF is NOT controlled
Ova
rian
resp
onse
Ovarian stimulation
? Hyporesponse = poor outcome
Hyperresponse = danger
Ovarian response prediction Female age AFC Body weight AMH
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AMH and its potential clinical applications
AMH
Fecundity
IVF
PCOS
POI
Menopause
Cancer treatment
Ovarian surgery
GC tumours
Anorexia
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Poor response (15)
AUC AMH 0.82
(28 studies; n=5.705 women)
F&S 2013
(57 studies; n=4.786)
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Steps towards individualised ovarian stimulation for IVF
Same starting dose of gonadotrophin to all patients associated with efficacy or safety concerns for some patients
Number of patients
Observed distribution Ideal curve
Number of oocytes
Risk of low efficacy
Risk of safety concerns and cancellation of transfer
Highest efficacy
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F&S 2017
Conclusion Individualised dosing More often desired oocyte No
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Complementary approaches - evidence vs patient based medicine
EBM Treatment focus
Multiple interventions
RCT Homogenous pt population
PBM Patient/context focus
Single intervention
Cohort, follow-up
Heterogeneous pt
Personalised medicine�in reproduction��Disclosure of interest, FauserThe era of personalised medicineDevelopments in clinical researchSlide Number 5Current evidence based �medicine paradigmSlide Number 7Slide Number 8Standard vs tailored approach in medicineParadigm shift from evidence based �to patient tailored medicine (2)Slide Number 11The EBM paradigm�Examples of personalised care �in infertilitySlide Number 14CC for ovulation induction in PCOSPrediction Medicine, methodologyCC ovulation induction in WHO 2�- outcome predictionSlide Number 18Ovarian stimulation for �IVF is NOT controlledAMH and its potential clinical applicationsSlide Number 21Steps towards individualised�ovarian stimulation for IVFSlide Number 23Complementary approaches�- evidence vs patient based medicine