GnRH Agonist Addition to Routine Luteal Phase Support in Assisted ...
Luteal phase support (LPS): dose ranging issues … Ziegler-2.pdf · dose ranging issues and new...
Transcript of Luteal phase support (LPS): dose ranging issues … Ziegler-2.pdf · dose ranging issues and new...
Luteal phase support (LPS): dose ranging issues and new perspectives
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
Paul Pitrea
Corine Menez
Bander Kuttbi
Ann Marszalek
Alessandra Fubini
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
The options existing and doses used
The needs for LPS
A sub-cutaneous P4 preparation
Non-pelvic effects of P4?
Luteal phase support (LPS): dose ranging issues and new perspectives
The options existing and doses used
The needs for LPS
A sub-cutaneous P4 preparation
Non-pelvic effects of P4?
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Defective luteal support in ART due to high hormone levels, GnRH analogues and hCG.
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
At time of luteo-placental shift or as early as the time of the positive pregnancy test.
On retrieval day or the day after, for minimizing UC at time of transfer. Earlier onset may advance closure of window of receptivity
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
The options existing and doses used
The needs for LPS
A sub-cutaneous P4 preparation
Non-pelvic effects of P4?
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Parenteral Oral Vaginal Transdermic
Poor bioavailability
Poor permeability
First described
Luteal phase support (LPS): dose ranging issues and new perspectives
P4 Oral P4: Not efficacious due to hepatic metabolism
Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism
IM SC
Luteal phase support (LPS): dose ranging issues and new perspectives
P4
IM SC
P4
first uterine pass effect
vaginal
Oral P4: Not efficacious due to hepatic metabolism
Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism
Vaginal P4: The only practical alternative to IM P4
Luteal phase support (LPS): dose ranging issues and new perspectives
P4
P4
first uterine pass effect
IM SC vaginal
0
5
10
15
20
25
30
0
0.2
0.4
0.6
0.8
1
1.2
Uterine tissue Serum levels
IM
IM vag
vag IM vs. vaginal No differences: why?
Oral P4: Not efficacious due to hepatic metabolism
Trans dermal P4: Not possible due to quantities (25mg/day) and skin metabolism
Vaginal P4: The only practical alternative to IM P4
Luteal phase support (LPS): dose ranging issues and new perspectives
P4 IM SC vaginal
IM vs. vaginal No differences: why?
P4
0
5
10
15
20
25
30
0
0.2
0.4
0.6
0.8
1
1.2
Uterine tissue Serum levels
IM
IM vag
vag
first uterine pass effect
Luteal phase support (LPS): dose ranging issues and new perspectives
Parenteral
First described
5/5/13
Luteal phase support (LPS): dose ranging issues and new perspectives
Doses
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Doses
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Doses
Hormone: P4
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
The options existing and doses used
The needs for LPS
A sub-cutaneous P4 preparation
Non-pelvic effects of P4?
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Parenteral Oral Vaginal Transdermic
Poor bioavailability
Poor permeability
First described
Luteal phase support (LPS): dose ranging issues and new perspectives
Vaginal Transdermic
cyclodextrin
New self-injectable P4 (25mg/d)
Luteal phase support (LPS): dose ranging issues and new perspectives
cyclodextrin
New self-injectable P4 (25mg/d)
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
cyclodextrin
25 & 50mg: 100% decidua-lized endomrium No difference between the 2 doses tested
25 50
de Ziegler et al. Fertil Steril 2013
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
New self-injectable P4 (25mg/d)
cyclodextrin
25 50
0
20
40
60
80
100
120
0 5 10 15 20
hours (day 11)
Pro
geste
ro
ne n
g/m
l
de Ziegler et al. Fertil Steril 2013
Sator et al. Gyn End 2013;29:205-8.
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
New self-injectable P4 (25mg/d)
cyclodextrin
25 50
de Ziegler et al. Fertil Steril 2013
Sator et al. Gyn End 2013;29:205-8.
AEs related to study drug: Nb of AEs recorded durigng the 14 days of treatment /tot Nb of injections per group (%)
0,00
10,00
20,00
30,00
40,00
50,00
60,00
70,00
Injection site
bruising
Injection site
erythema
Injection site
redness
Injection site
swelling
Other Total
AE
s/N
b o
f in
jecti
on
s (%
)
Prog IBSA 50 mg IM
Oily Prog 50 mg IM
tolerability
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
New self-injectable P4 (25mg/d)
Physiology: production of progesterone = 25 mg/day
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Physiology: production of progesterone = 25 mg/day
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
LH
P4
P4: pulsatile production under the control of LH:
5ng/mL
Day LH +10
Physiology: production of progesterone = 25 mg/day
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
The options existing and doses used
The needs for LPS
A sub-cutaneous P4 preparation
Non-pelvic effects of P4?
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
01020304050
P <0.0001
Crinone IM P4
Luteal phase support (LPS): dose ranging issues and new perspectives
There appears to be a superiority of IM over vaginal progesterone for frozen embryo transfers (FET)
The difference may result from non-pelvic effects of progesterone (immuno-suppression and/or Vasopressin/oxytocin)
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
LPS is necessary in ART because CL support by LH is deficient
Progesterone production during the luteal phase is of ~25ng/mL
A new sub cutaneous progesterone preparation is available: Prolutex (25mg/day)
Endometrial effects of vag and injectable progesterone are equivalent.
In FET, injectable progesterone results in higehr PR possibly, through non-pelvic effects.
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
Paul Pitrea
Corine Menez
Bander Kuttbi
Ann Marszalek
Alessandra Fubini
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
P4: pulsatile production under the control of LH:
Day LH +8 LH
P4
Physiology: production of progesterone = 25 mg/day
Luteal phase support (LPS): dose ranging issues and new perspectives
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Université
Paris-Descartes,
Hôpital
Cochin Paris,
France
Luteal phase support (LPS): dose ranging issues and new perspectives