Prof.Dr. Bart CJM Fauser

Personalised medicine in reproduction

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

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

Developments in clinical research

2016

JAMA 2014

Current evidence based medicine paradigm

Patie

nt p

opul

atio

n

A

B

EBM

95% CI difference

2014

2014

Standard vs tailored approach in medicine

Herceptin, Breast cancer

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

2015

The EBM paradigm

Meta analysis

experimental

observational

IPD Meta analysis

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)

Hunault model Habbema, Hum Reprod 2015 Hunault, Hum Reprod 2005 Hunault, F&S 2002 Eimers, F&S 1994 Collins, F&S 1989

CC for ovulation induction in PCOS

Ovulation

Pregnancy (35-40%)

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

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

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

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

AMH and its potential clinical applications

AMH

Fecundity

IVF

PCOS

POI

Menopause

Cancer treatment

Ovarian surgery

GC tumours

Anorexia

Poor response (15)

AUC AMH 0.82

(28 studies; n=5.705 women)

F&S 2013

(57 studies; n=4.786)

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

F&S 2017

Conclusion Individualised dosing More often desired oocyte No

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