gnrh costeffectiveness
TRANSCRIPT
COST EFFECTIVENESS
ANALYSIS: GNRH
AGONIST VS ANTAGONIST
kasr al ainy school of MedicineCairo University
16 follicles
12 mature eggs
14 eggs
Extras frozen if good
2 to 5 transferred9 fertilize normally
5 divide normally
30-40% of couples
4 stop dividing
& sperm
IVF/ICSI : Typical progression
DeliveryPregnancyEmbryosEggs
Influences on quality:
* Maternal age
* Prior quality
Influences on quantity:
* Ovarian reserve
* Strength of stimulation
--LH tone
--Metformin use
--OC pretreatment
--GnRH analog use
--Gonadotropin dose
--hCG administration
Maturity of eggs
Sperm supply
Fertilization
Culture condition
Quality of embryo
Health of embryo
Day of transfer
Method of transfer
Number transferred
Luteal support
Quality of embryo
Health of embryo
Health of sperm
Luteal support
IVF-MANY FACTORS AFFECT OUTCOMES
HOW TO MAKE DECISION ABOUT
DRUG
+
2008
PROTOCOLS FOR IVF
GnRH Antagonist
Protocols
GnRH Agonist
Protocols
225 IU per day
(150 IU Europe)Individualized Dosing of FSH/HMG
250 mg per day antagonist
Individualized Dosing of FSH/HMG
GnRHa 1.0 mg per day
up to 21 days0.5 mg per day of GnRHa
225 IU per day
(150 IU Europe)
Day 6
of FSH/HMG
Day
of hCG
Day 1
of FSH/HMG
Day 6
of FSH/HMG
Day
of hCG
7 – 8 days
after estimated ovulation
Down regulation
Day 2 or 3
of menses
Day 1
FSH/HMG
AIM OF THIS TALK
To conduct cost effectiveness analysis between
GnRH agonist vs antagonist in IVF/ICSI cycles
AL-INANY & ABOULGHAR, 2001
AL-INANY ET AL., 2006
O.R = 0.82, 95% CI = 0.68 to 0.97
CPR
(AL-INANY ET AL, 2011)
LIVE BIRTH RATE
OHSS (AL-INANY ET AL, 2011)
OHSS
OHSS in agonist group: 3.74% (84/3165)
OHSS in antagonist group: 1.91% (149/ 2252)
MISCARRIAGE RATE
IN FAVOR OF ANTAGONIST
much shorter duration of GnRH analogue
treatment (OR -20.90, 95% CI -22.20 to -
19.60)
less days of stimulation (OR -1.54, 95% CI -
2.42 to -0.66).
reduction in the amount of gonadotrophins
(OR -4.27, 95% CI -10.19 to 1.65)
HOW TO CALCULATE CE IN IVF
Needs large sample size (~1000 women to get reliable estimate of CE)
Needs accurate data as possible
Needs to consider uncertainty
So computer modeling is the best alternative
UNCERTAINTY
IVF/ICSI cycle involves numerous steps each has its outcome probabilities and associated uncertainties
Therefore, it should be considered in the model
EXAMPLE COHORT “EXPECTED VALUE”
ANALYSIS: FOR 1000 WOMEN
Start Cycle
1,000
Ovum Pickup
No OHSS
Ovum Pickup
OHSS
981
19
Fertilization
& Transfer
No Oocytes
38
962
Clinical
Pregnancy
-ve βHCG
298
664
Ongoing
Pregnancy
Miscarriage
40
258
325
34
Continue
Stop
Goal!
IT IS NOT ONLY ONE CYCLE Many patients achieve pregnancy sometimes up to
10 or more cycles of treatment,
However, financial and other personal cost often
limit most patients to only 3 cycles of treatment
ACCORDINGLY
The recurring nature of ART events/cycles dictated the building of a state transition model, also called a Markov model, which is by definition designed to mimic recurring events
A Markov model was built to simulate the IVF treatment cycle with its key steps
ANALYTICAL METHODS
Monte Carlo micro simulation were used to examine the potential impact of assumptions and other uncertainties represented in the model
Monte Carlo simulation, can incorporate all parameter uncertainties
TreeAge Pro software was used to model and analyze our problem
Miscarriage
p_miscar_Start Cycle
Pregnancy
#Ongoing Pregnancy
Clinical Pregnancy
p_clin_preg_
continue
#Start Cycle
stop
t_discon_nomed[ _stage]Stop IVF
-ve bHCG
#
Fertilization &Embryo Transfer
#
No Oocytes
p_cancel_Start Cycle
Ovum PickupNo OHSS
#
Miscarriage
p_miscarStart Cycle
Pregnancy
#Ongoing Pregnancy
Clinical Pregnancy
p_clin_preg_
continue
#Start Cycle
stop
t_discon_nomed[ _stage]Stop IVF
-ve bHCG
#
Fertilization &Embryo Transfer
#
No Oocytes
p_cancel_Start Cycle
Ovum PickupOHSS
p_OHSS
Start Cycle1
Ongoing Pregnancy0
Stop IVF0
Agonist
Miscarriage
p_miscar_Start Cycle
Pregnancy
#Ongoing Pregnancy
Clinical Pregnancy
p_clin_preg
continue
#Start Cycle
stop
t_discon_nomed[ _stage]Stop IVF
-ve bHCG
#
Fertilization &Embryo Transfer
#
No Oocytes
p_cancel_Start Cycle
Ovum PickupNo OHSS
#
Miscarriage
p_miscarStart Cycle
Pregnancy
#Ongoing Pregnancy
Clinical Pregnancy
p_clin_preg
continue
#Start Cycle
stop
t_discon_nomed[ _stage]Stop IVF
-ve bHCG
#
Fertilization &Embryo Transfer
#
No Oocytes
p_cancelGStart Cycle
Ovum PickupOHSS
p_OHSS
Start Cycle1
Ongoing Pregnancy0
Stop IVF0
antagonist
Start cycle
IVF MODEL COSTS AND UNITS
Name Description cost EGP
c_OPU/ET Ovum pickup 6500
c_OHSS Severe OHSS Management
7,100
c_Miscar Miscarriage 1,500
c_bHCG One βHCG test 60
c_Investigations Lab inv. 720
c_US Ultrasound 250
IVF MODEL COSTS AND UNITS
Name Description cost EGP
c_GnRHa * GnRHa unit cost 38
u_GnRHa † units GnRHa required 28
c_GnRHant * GnRHant unit cost 210
u_GnRHant † units GnRHant required 4
c_LP_support* Leuteal phase support 470
* MOHP list price
IVF TRANSITION PROBABILITIES
Name Description Value
p_cancel_agonist 1 Probability of cancellation for fear of OHSS
0.038
p_cancel_antagonist 1 Probability of cancellation for fear of OHSS
0.019
p_clin_preg_agonist 1 Probability of clinical pregnancy 0.310
p_clin_preg_Anta 1 Probability of clinical pregnancy 0.269
p_OHSS_agonist 1 Probability of severe OHSS 0.038
p_OHSS_Anta 1 Probability of severe OHSS 0.019
1 Al-Inany, et al. 2011
IVF TRANSITION PROBABILITIES
Probability of
discontinuation at the
end of the cycle (failed
clinical pregnancy) for
non-medical reasons 1
Cycle Value
1 0.489
2 0.524
3 0.571
1 Schröder et al. Cumulative pregnancy rates and drop-out rates in a
German IVF programme: 4102 cycles in 2130 patients. May 2004
RESULTS:
GnRHa cycle costs on average 42588 EP per
pregnancy, with a final 47% chance of achieving
pregnancy after 3 cycles, versus an average of
EGP 46370 per pregnancy, and a final 39.6%
chance for GnRH antagonist
FOR 1000 WOMEN : COST
GnRHa 4258496
4637527GnRHant
47.1% CPR
39.6% CPR
FURTHER ANALYSES
Incremental Cost = 379031
Incremental Effectiveness =
7.5%
ICER=5,053,746 (account for more
than 118 cycles)
SO OUR CONCLUSION:
Based on Cochrane meta-analysis GnRH agonist
seems to be more cost effective than GnRH
antagonist
