Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Charlers Chapron Bruno Borghese

Hervé Foulot

Amin Bititi

Paul Mazurk

Guillaume Pierre

Marie Christine Lafay

Fouzia Decupere

François X. Aubriot

Dominique de Ziegler Vanessa Gayet

Pietro Santulli

Rebecca Monffat

Blandine Boquet

Anna Raggi

Paul Pitrea

Bander Kuttbi

Corine Perez

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The future is not what it used to be any more

Yogi Berra

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The future is not what it used to be any more

Yogi Berra

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The future is not what it used to be any more

Yogi Berra

Why did somebody fail ART?

Bad luck

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The future is not what it used to be any more

Yogi Berra

Bad luck Embryo- endo dysynchrony

Why did somebody fail ART?

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Antagonist protocol

Shorter, less injections, lower OHSS risk

More demanding (experience), no synchronization

Pro

Con

Oocytes Embryos

Humaidan et al. HRU 2011;17:734-40.

Lupron (GnRH-a) trigger

GnRH-a toxic luteolisis

Oocytes Embryos

Donor-egg ART

recipients

Bodri D et al.

E2 priming Implantation

Humaidan et al. HRU 2011;17:734-40.

Lupron (GnRH-a) trigger

GnRH-a toxic luteolisis

Oocytes Embryos

Humaidan et al. HRU 2011;17:734-40.

Implantation

Donor-egg ART

recipients

Bodri D et al.

E2 priming Implantation

Humaidan et al

vag. P4

Lupron (GnRH-a) trigger

GnRH-a toxic luteolisis

Lupron (GnRH-a) trigger

Oocytes Embryos

Humaidan et al. HRU 2011;17:734-40. ?

Donor-egg ART

recipients

Bodri D et al.

E2 priming Implantation

Engmann et al

Implantation

Engmann et al. FS 2012;97:531-3.

IM P4

Implantation

Humaidan et al

vag. P4

GnRH-a toxic luteolisis

At Cochin, because progresses with embryo vitrification, we differ transfers in case of GnRH trigger

Two options

Add small 1,500IU of hCG

Vitrify all and differ ET

Humaidan P et al

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The bottle neck of ART

Bad luck Embryo-endo

dysynchrony

Why did somebody fail ART?

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

oocytes zygotes Blastocysts D2-3

Cannot select

May not make it to B

Effective vitrification

Effective vitrification

Vitrification of embryos ~100% efficacy

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

What are the possible option?

The bottle neck of ART

Endo receptivity w/ E2 & P4: optimal

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France The bottle neck of ART

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The differed ET option (Dif-ET)

The bottle neck of ART

the GnRH triger option

Parenteral Oral Vaginal Transdermic

Poor bioavailability

Poor permeability

First described

Hormonal preparation for frozen embryo transfers

Hormonal preparation for frozen embryo transfers

Parenteral Oral Vaginal Transdermic

Poor bioavailability

Poor permeability

First described

cyclodextrin

LPS: New self-injectable P4 (25mg/d): Prolutex®

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

62

50

35

23

20

11 ≥7 zygotes

DETproposedn=62

n=50

AntagonistProtocolandfinaloocytesmaturationwithTriptorelin ITT-population

Differenttreatmentn=12

-AntagonistProtocolandfinaloocytesmaturationwithhCGn=6

-MicroflareProtocoln=6

n=15ITTpopulation Notmettheinclusioncriteria

n=35PPpopulation

n=23≤62PNn=1≥72PN

Figure 1. Disposition of the patients proposed for DET

n=11≥72PN

n=20firstDay2transferperretrievial

n=9firstblastocysttransferperretrievial

n=4postponedtransferformedicalandpersonalreason

n=2noblastocystavailablefortransfer

Anna Raggi

23 ≤6 zygotes

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

COS characteristics

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

7

10

13

day hCG

10.2 10.7 11.2

COS characteristics

*

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

Tot FSH (IU)

COS characteristics

400

2400 2243 2213 2271

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

E2 d-hCG

0

500

1000

1500

2000

2500

3000 1820 2339 2660

COS characteristics

* *

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

# MII

COS characteristics

0

2

4

6

8

10

12 8.0 8.2 9.6

*

Cases

Controls #1

Controls #2

Age- and rank-matched

Age-matched and rank =1

≥2 ART failures

# 2PN

COS characteristics

0

4

8 5.5 5.6 6.6

NS NS

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Anna Raggi

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Anna Raggi

cPR/ET

0

20

40

60

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Anna Raggi

Outcomes of ITT and PP population

ITT population

(n=50)

PP population

(n=35) Clinical characteristics Age 35±4 33.1±3.1 Rank 3.8±1.1 4±1.1 ART-Outcomes Retrievals 50 35Fertilization rate (%) 71 72Nr of Transfers 37 29Clinical pregnancies/ retrievial (rate,%) 16(32) 14(40) Clinical pregnancies/ transfer (rate,%) 16(43.2) 14(48.3) Ongoing Pregnancies/ transfer (rate,%) 14(37.8) 12(41.4) Transferred Embryos 66 52 Fetal hearts (implanation rate,%) 17(29.3) 15(32.2)

cPR/ET

0

10

20

30

40

50

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

The differed ET option (Dif-ET)

5 extra weeks

Eextra visit

Extra work, Extra $$$

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Antagonist protocol provide similar pregnancy rates, but are ‘softer’ on the patients and are less prone to cause OHSS

Can be synchronized with the OC pill. Requires then to use some hMG (Merional®)

Offer the GnRH trigger option, which avoids all risk of OHSS

With the GnRH trigger option, one should either:

Add small amounts of hCG at the time of oocyte retrieval (1,500IU), as per Humaidan.

Opt for a freeze all option with vitrification of embryos on either day 1 or 5-6 (balstocyst).

The GnRH trigger option, offers ‘no-hCG’ ART (VTE risk, Obstetrical outcome)

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Improved implantation

OB risk in FET: reappraisal

Decrease preg associated VTE risk

Université

Paris-

Descartes,

Hôpital

Cochin

Paris,

France

Charlers Chapron Bruno Borghese

Hervé Foulot

Amin Bititi

Paul Mazurk

Guillaume Pierre

Marie Christine Lafay

Fouzia Decupere

François X. Aubriot

Dominique de Ziegler Vanessa Gayet

Pietro Santulli

Rebecca Monffat

Blandine Boquet

Anna Raggi

Paul Pitrea

Bander Kuttbi

Corine Perez