1- TAYFUN BAĞIŞ – IVF`te GnRH Antagonistleri

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Prof. Dr. Tayfun Bagis
Acıbadem University

The 2 studies had different results for
pregnancy outcomes
Live Birth Rate* in Meta-analyses,
GnRH Antagonists vs GnRH Agonists
Al-Inany1
Kolibianakis2
0.82
0.86
95% CI
0.69-0.98
0.72-1.02
P value
0.03
0.085
OR
*Live birth rate included ongoing pregnancies (Al-Inany) or calculated rates (Kolibianakis).
OR = odds ratio.
1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.
2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.
Characteristic
Al-Inany1
Kolibianakis2
Last date searched
Feb 2006
Dec 2005
No. of studies included
27
22
Included non–peerreviewed data
Yes
No
Included studies on IUI
Yes
No
3,865
3,176
Ongoing pregnancy
or live birth rate
(Only 15 studies evaluable,
n=2,973)
Live birth rate*
(All 22 studies included;
in 12/22 studies, live births
estimated)
Total patients
Primary outcome
IUI = intrauterine insemination.
*Ongoing pregnancies were converted to live birth equivalents. Live births = 84% of number viable at week 7
or 92% of number viable at week 12 of gestation.
1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.
2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.
Al-Inany1
Kolibianakis2
Duration of analog
treatment
−20.90 days
(95% CI −22.20, −19.60)
−19.48 days
(95% CI −21.05, −17.91)
Duration of ovarian
stimulation
−1.54 days
(95% CI −2.42, −0.66; P=0.0006)
−1.13 days
(95% CI −1.83, −0.44)
Risk of
severe OHSS
OR 0.61
(95% CI –0.42, 0.89; P=0.01)
RR 0.46*
(95% CI 0.26, 0.82; P=0.01)
Interventions
to prevent OHSS
OR 0.44
(95% CI 0.21, 0.93; P=0.03)
*For every 59 women treated with a GnRH agonist vs GnRH antagonist, 1 additional case of severe OHSS
will occur.
RR = risk ratio.
1. Al-Inany et al. Cochrane Database Syst Rev. 2006;3:CD001750.
2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.
LH rise
LH surge
Kolibianakis2
OR 8.27
(95% CI 3.82-17.90)
OR 4.05
(95% CI 1.53-10.72)
2. Kolibianakis et al. Hum Reprod Update. 2006;12:651.
Siklus öncesi problemler
Senkronizasyon (oosit sayısı)
Fleksibilite (hafta sonu plan)
Progesteron
OKS
Estrogen
OCP pre-treatment
Rate difference in ongoing pregnancy per woman:
-5% (95% CI: -10 to -1), p = 0.02
1. Griesinger et al. Fertil Steril. 2008:90;1055-1063.
2. Update Griesinger et al. submitted
Siklus başındaki problemler
Gn ne zaman başlanmalı (2-3)?
Korpus luteum rescue (P4 yüksekliği)
D2 P4 ölçümü
Problems at the beginning of cycle.

Cycle day 2
Transvaginal US +
(if desired) hormonal profile
Ongoing PR
Per started cycle
Normal-P
High-P
group
group
31.8 (124/390)
5 (1/20)

P
0.011
Per oocyte
retrieval
Per ET
33.8 (124/367)
6.3 (1/16)
0.026
36.9 (124/336)
6.3 (1/16)
0.014
Ongoing IR
Progesterone on
HCG day
21.1 (151/714)
1.1 (0.8)
3.6 (1/28)
1.2 (1.3)
0.028
NS
Kolibianakis 2004
ACIBADEM EXPERIENCE
A
N=102
MODA
N=66
P
Female age
32.02±4.9
31.74±4.8
0.711
Duration of infertility (years)
4.3±3.1
3.9±3.3
0.444
BMI (kg/m2)
24.07±4.3
23.4±3.6
0.374
Gravida
0.64±1.03
0.37±0.8
0.077
Cycle no
1.63±0.90
1.92±1.29
0.102
Antral follicle count
13.6±6.4
14.6±5.3
0.381
ANT
N=20
MODA
N=20
P
Total gonadotrophin dose
1829.7±734
1661.2±482
0.116
E2/HCG day
1483.1±1319.9
1858.9±1452.5
0.140
P/HCG day
0.68±0.33
0.84±0.46
0.032
Endometrium/HCG day
10.9±2.07
11.2±2.59
0.419
No. Follicle >10mm/HCG
11.05±5.8
12.64±5.27
0.091
14
12
10
4.01
5
17-22 mm
8
6
3.6
4.09
3.8
3.9
4
2
0
Antagonist
MODA
14-16 mm
10-13 mm
P/HCG day
≥ 1.2
A
% 6.8
MODA
%16.4
P
0.108
11.3
12
10
8.6
8
8.6
6.7
6
6.11
5.8
4.7
4
4.6
2.3
2.8
2
0
Oocyte no
MII oocyte no
Cleavage no
Grade I no
Total embryo no
ANT
MODA
HCG (+)
70
61
60
50
47.4
40
36/59
30
20
50/95
10
0
A
MODA
OR 1.409 CI %95 (0.728-2.726)
HCG (+)
Antagonist başlama problemleri
SD 4? SD5? SD6? Fleksible?
Siklus başından itibaren?
Modifiye protokoller?
Antagonist dozu?
1- At least one follicle measuring >14 mm
2- Estradiol levels >600 pg/ml
3- LH levels >10 IU/l
Retrieved oocytes
12.1
MII %
75.8
Fertilization %
58.7
ET number
1.9
Cryo number
2.4
Ongoing IR %
26.5
Ongoing PR/Cycle
39.7
Ongoing PR/Retri
39.7
Ongoing PR/ET
42.4
12
10
10
8.8
9.3
8.6
8
0,25
6
5.4
4.6
5.3
0,5
4.9
4
3.3
2.5
3.3 3.5
2
0
oocyte no
embryo no
good qe
The Ganirelix dose-finding study group. Hum Reprod. 1998.
1
2
The Ganirelix dose-finding study group. Hum Reprod. 1998.
40
37.1
35
30
25
20
15
13
0,5
15.3
13
9 8.8
10
5
0
0,25
21.9
1.5
0.1
OPR/ET
8.5
IR
1.6
3.7
Early miscar
1
2
Upper
quartile
Middle
quartile
Lower
quartile
P
Oocyte yield
15.2 (7.5)
13.1 (7.9)
11.8 (5.6)
<0.01
CPR
45.9
28.7
25
0.01
LBR
38.6
22.3
20
0.02
E2 response (defined as posttreatment/pretreatment E2 ratio)
HCG günü problemler
HCG günü antagonist?
HCG kriterleri?
HCG ertelenebilir mi?
HCG günü P4?
PHASE III TRIALS
LH rises (≥10 IU /L) with
concomitant progesterone
rises (>1 ng/mL)
European trial
1.5%
North American trial
1.5%
European and Middle
East trial
GnRH agonist control
group (pooled data)
0.4%
0.8%
No of patients (%)
CPR/ET
LBR
Premature
luteinization
p≥1.2 ng/ml
No Premature
luteinization
P<1.2 ng/ml
31/81 (38.3%)
50/81 (61.7%)
P
8/31 (25.8%)
27/50 (54%)
0.01
12/87 (13.8%)
41/128 (32%)
0.007
Overall prevalence of premature luteinization was 18.2 %.
(P>1.5 ng/ml)
Luteal faz problemler
Vaginal & IM Progesteron?
GnRH agonist suplementasyonu?
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