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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