which is better afc or amh

7/22/2019 Which is better AFC or AMH

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David Seifer, MD

Genesis Fertility & Reproductive Medicine

Brooklyn, New York

The content of this presentation not intended as medical advice and does not represent and

exhaustive treatment of the subject matter.

2013 Ferring B.V.1


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Which is better to assess ovarian reserve: AFC or AMH?

Introduction - 10 mins

AFC - 10 mins

AMH - 10 mins

Q&A 10 mins

Dr. John Frattarelli

Fertility Institute of HawaiiHonolulu, Hawaii

Dr. Richard Fleming

Glasgow Center for Reproductive Medicine (GCRM)

Glasgow, Scotland


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DISCLOSURE

Dr. Seifer receives royalties from a licensing agreement betweenUMDNJ/MGH and Beckman Coulter for the use of MIS/AMH in

determining ovarian reserve.


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Question 1

Are you a

a. Nurse

b. Nurse practitioner

c. REI subspecialist

d. Ob/Gyn Generalist


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Please make your selection...

5

1 2 3 4

14%

34%

52%

1%

1. Choice One2. Choice Two

3. Choice Three

4. Choice Four


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Question 2

Do you practice in

a. US/Canada

b. Europe

c. Asia

d. Australia

e. South America


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7

1 2 3 4 5

27%

43%

23%

0%

7%


3. Choice Three

4. Choice Four

5. Choice Five


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9

1 2 3 4

5%

79%

8%8%


3. Choice Three

4. Choice Four


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Question 4

What would you choose if you could only use a single test toassess ovarian reserve?

a. AFC

b. AMH

c. FSH


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11

1 2 3

39%

13%

47%1. Choice One

2. Choice Two

3. Choice Three


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The Biology of Egg Supply

Women begin with lots of eggs, then run out.

At birth ~2 million eggs

At first period, ~400,000 eggs (lose ~1000/period)

At 50, ~400 eggs

Cross Section of Ovary


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ROC and meta analyses demonstrate that onlyAMH andAFC* candistinguish between 4 principle categories of response and eggyields (non, poor, normal, excessive).

Broekmans et al. Hum Reprod Update, 2006

Broer et al. Fertil Steril, 2009

La Marca et al. Hum Reprod Update, 2010

* greater inter-operator variation, greater intra-cycle and inter-cycle variation than AMH particularly in overweight

and obese women.


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20


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21


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Pretreatment transvaginal ultrasound examinationpredicts ovarian responsiveness to gonadotrophins

in in-vitro fertilization

Tomas et al. Hum Reprod 1997


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Use of the antral follicle count to predict the outcome

of assisted reproductive technologies

Chang et al. Fertil Steril 1998


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Why use AFC?

To predict outcomePoor response

Cancellation

Hyperresponse

Normal response

Pregnancy

Live Birth

To help individualize treatment


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Basal antral follicle number and mean ovarian diameterpredict cycle cancellation and ovarian responsiveness in

assisted reproductive technology cycles

Frattarelli et al. Fertil Steril 2000


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Antral follicle count in the prediction of poor ovarian responseand pregnancy after in vitro fertilization: A meta-analysis and

comparison with basal follicle-stimulating hormone level.

Hendriks et al. Fertil Steril 2005


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Antral follicle count in clinical practice: analyzingclinical relevance

AFC

helpful in determining

stimulation protocol

determinant of oocytes

retrieved per starting FSH

dose

predicts ovarian response,

not embryo quality or

pregnancy

Hsu et al. Fertil Steril 2011


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Prediction of in vitro fertilization outcome atdifferent antral follicle count thresholds in a

prospective cohort of 1,012 women

0

10

20

30

40

50

310 1115 1622 >22

LiveBirthRate

Antral Follicle Count

Jayaprakasan et al. Fertil Steril 2012


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Prediction of an excessive response in in vitro fertilization frompatient characteristics and ovarian reserve tests and comparison

in subgroups: an individual patient data meta-analysis

Broer et al. Fertil Steril 2013


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Role of baseline antral follicle count and anti-Mullerian hormone inprediction of cumulative live birth in the first in vitro fertilisation cycle:

a retrospective cohort analysis

Li et al. PLoS One 2013


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Most studies suggest similar predictive value withand a positive correlation between AFC or AMH

Broekmans et al. Hum Reprod Update 2006

El-Din et al. Med J. Cairo Univ 2011

Panchal et al. J Hum Reprod Sci 2012

Lukaszuk et al. Eur J Obstet Gynecol Reprod Biol 2013

Li et al. PLoS One 2013


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Rational for using AFC

As predictive as any ovarian reserve test

Easy to use

Non-invasive

Ubiquitous Immediate and repeated results

Personalize

Lack of superiority of any ovarian reserve test


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Conclusion

AFC is an easy readily accessible tool for

the REI that helps to predict IVF cyclestimulation and outcome

33


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The Case for AMH

Richard Fleming, PhD

GCRM, Glasgow, Scotland

34

Or, why settle for second best?

The content of this presentation is not intended as medical advice and does not represent

and exhaustive treatment of the subject matter. 2013 Ferring B.V.


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AMH and AFC& Functional Ovarian Reserve

AMH Represents the number of

granulosa cells in growing

follicles. All are active.

Single assay with good

performance in NEQAS

Issues of standardization

AFC Identifies small follicles FSH

sensitive and also atretic

follicles.

Multiple technological sources,

and lack of consensus

Issues of training


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AMH versus AFC overview

Normal Population

Well Defined

Clinically valuable

Normal Population

Well Defined

Clinically valuable

Normal Population

Well Defined

Clinically valuable

Inappropriate

Normal Population

Data - Negligible

Frequently

Inappropriate

Normal Population

Data - Negligible

Technical

Variance

Normal Population

LACKS CONSENSUS

Juvenile Adolescent Reproductive Years

AFC

AMH


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Categories of ovarian responseAMH concentrations (DSL Assay)

AMH: Close to 50% of the variability in egg yields is due to AMH

Nelson SM et al, Human Reprod, 2007

0.7

1.42.1

2.8

3.5

4.2

Normal

C

Non

A

Poor

B

Excessive

D

0 or

Cancel1 - 4 5 - 19 >20Eggs 1.1

2.5

AMHng/ml

Pragmatic

Discrimination

PotentialExcess

SafeReduced

AMH(ng/ml)


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A randomised study with post hoc analyses of eggyields and cumulative pregnancy

Megaset Study: (N= 749 patient cycles; 21 to 34y) randomised rFSH or HP-hMG (150IU daily);

GnRH Antagonist control; Single blastocyst transfer

1.4

2.8

4.2

5.6

7.0

19

AMHng/ml

Egg Yields

Correlation of AMH

with Egg Yield:

r = 0.55;

p


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Egg Yields: AMH & AFC

5

10

15

20 AFC

19

Egg YieldsCorrelation: AMH with Egg yield:

r = 0.55; p


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We can convince ourselves that Black is White

Martnez F et al, 2013: letter challenging the findings of Arce JC et al,

Fertil Steril, 2013.

They suggested that within each centre the AFC may perform equally

well . . .

Reply with analyses within each centre*:

AMH was consistently found to be superior at the level at the

individual clinics.

When analyzing clinics enrolling 10 patients 16 of 18 clinics had numerically higher correlation

coefficients with AMH than AFC.

* Arce JC et al, Fertil Steril, 2013


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AMH and AFC - Conflicting Cases:Single Centre Analysis

1. Highest Risk Predicted low response (but in reality a

high responder) treated with

maximizing protocol

2. Most Inconvenient Predicted high response (but in reality a

poor responder) treated with mildprotocol


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Low AMH (< 1.5 ng/ml) + High AFC (> 18)

Cases

3 in 559

Days Stim

11 (Av=9)

OPU %Cases

100

Eggs

6.7

Incidence is rare

Egg yield: Average for the AMH group is 4.1:

- no risk identified

Predicted low response treatedwith maximizing protocol

1. Highest Risk


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High AMH (>3 ng/ml) + Low AFC (0 to 10)

Cases:248 in 1008

(24%)

Days Stim10.5 (Av=10)

OPU %Cases98

Eggs8.7

AMH cohort

average

8.8Incidence of this conflict is commonplace

Egg yield: Average for the AMH group

Suggestive that AFC may be misleadingly low in some cases

Predicted High response treatedwith mild protocol

2. Most Inconvenient


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IVF can be made safer when protocol isdictated by AMH

44

17 Eggs

Egg Number

9 EggsGCRM

Curve shift to left:

- Maximum LB achieved at loweregg numbers IVF made safer

Sunkara SK et al, 2011400,135 cycles (HFEA)Risk of OHSS

What is the effect of

reducing egg yields (mild

protocol) in women withhigh AMH?

Sunkara SK et al, Human Reprod, 2011


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BUT MY AMH IS AMAZING,

AND IF I LIKE, I CAN TAKE IT TO

ANOTHER DOCTOR !

I THINK MY DOCTOR FANCIES ME -

HE SAID HE COULDNT SEE A

SINGLE FOLLICLE


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Question 5

What would you choose if you could only use a single test to

assess ovarian reserve?

] a. AFC

b. AMH

c. FSH


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47

1 2 3

18%

1%

81%

1. Choice One

2. Choice Two

3. Choice Three


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Questions?

48

which is better afc or amh

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