This document discusses how 4P medicine, which stands for prevent, predict, personalize, and participate, is coming to assisted reproductive technology (ART). It provides several examples of using anti-Müllerian hormone (AMH) levels to predict ovarian response, egg yield, live birth rates, and complications in order to personalize and optimize IVF treatment plans and outcomes. The goal is to prevent complications, predict outcomes, personalize treatment protocols based on AMH and other factors, and encourage patient participation through healthy lifestyle changes.

1. 4P Medicine comes to ART
Prevent
complications
Predict
outcomes
Personalize
treatment
Participation
by patients

2. Predict live birth
 Ovarian reserve
 Age
 Cause of infertility
 Smoking status
 Duration of infertility
 Obstetric history
 IVF history
 Pharmacodynamics
 BMI
Nelson and Lawlor PLoS Med.
2011 Jan 4;8(1):e1000386.
IVFpredict.com

3. Predict oocyte yield and ovarian response by AMH
Nelson, et al Hum Reprod. 2007

4. Predict live birth with AMH
La Marca and Nelson et al Reprod Biomed Online. 2011
If you think of “predict” in conventional
terms of low medium, or high risk
Age (years)
AMH (ng/mL)
<0.4 0.4 – 2.8 ≥2.8
>37 0.05 (0.01 to 0.16) 0.18 (0.12 to 0.26) 0.29 (0.17 to 0.44)
31 – 37 0.09 (0.02 to 0.24) 0.27 (0.21 to 0.35) 0.40 (0.28 to 0.54)
<31 0.13 (0.04 to 0.36) 0.38 (0.26 to 0.51) 0.52 (0.38 to 0.67)
*Values in parenthesis are 95% confidence intervals

5. Predict live birth and oocyte quality with AFC
<34 34-38 34-38
Holte et al Fertil Steril 2011
OR 1.23 (95% CI 1.10, 1.37)

6. Predict complications
Nelson, et al. Hum Reprod. 2009
Normal Response
Reduced Response
Negligible Response
High Response
1.0
5.0
15
AMH
‘Normal’
& SAFE
Maximal Recruitment
Advantageous?
Risk of OHSS
increased
Excess burden
Few eggs
Long course
Agonist control
SAFE - BUT
Reduced Recruitment
Dis-advantageous?
Mild stimulation
Antagonist control
Risk of OHSS
decreased
Reduced burden
Lower egg yield

7. Personalizing treatment - AMH stratification
10
20
40
Protocol
Mild strategy
Antagonist Control
HCG Trigger
Mild strategy
Antagonist Control
Agonist Trigger
Long Down-regulation
Agonist Control
Flare Agonist
Age (y)
3025 35 45
50
AMH
(pmol/L)
50
50
40
30
20
10
70
40
Excessive
High
Normal
Reduced
Response Category
Nelson, et al. RBM Online 2012

8. Personalize treatment and prevent complications
2
4
6
8
10
12
14
16
EggYield
Reduced AMH
Antagonist
1 – 4.9
Pmol/L
Normal
Agonist
5 – 15
Pmol/L
Centre1 Centre 2
High AMH
>15
Pmol/L
Antagonist
P < 0.001
10
20
30
Antagonist
%Cycles
HighAMH
>15
Pmol/L
P < 0.001
Reduced OHSS
Excessive response
Nelson, et al. Hum Reprod. 2009

9. Personalize the number of embryos transferred
Nelson, et al. Lancet 2012

10. Participation of patients in healthy living
Mackay, Nelson, et al. PLOS Med 2012