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Mark Leondires, USAMark Leondires, USAReproductive Medicine Associates of CPReproductive Medicine Associates of CPNorwalk, USANorwalk, USA
Declared participation in a sponsored speaker´s bureau: for Merck Serono andOrganon. Declared that during the conference, he will explain if his presentationincludes discussion of any off-labeled or otherwise non-approved uses of anyproduct
Mark Leondires, MDMedical Director RMA of CT
How to optimize their use in ovarian hyperstimulation
Variables in Stimulation
PatientsGonadotropinshMG, hFSH, rFSH, ld hCG, rLH
AntagonistsAgonistsInduction of ovulationLuteal support
Patients
Normo-ovulatoryAge < 38Age = 38-42Age > 42Normal or diminished ovarian reserve
AnovulatoryPCOSHypothalamic dysfunction
Gonadotropins
hMG vs FSHFSH+ hMG+ ldhCG
Choice of regimen program specificProper dosing based on age, history, and
previous stimulation
Agonists
First used in 198o’s*Prevents premature ovulationOptionsLong-protocolMicro-dose flare protocol
Alternative usage for trigger in OHSS highrisk patients for use with antagonist cycle
* Jennings JC et al. (1996) Drugs.
Agonists
LeuprolideBuserelinGoserelinTriptorelin
Associated with initial flare and thenpersistent suppression of endogenouspituitary secretion protecting from prematureLH surge
Agonist - OptionsLong protocolDay 21 or OCP overlap
Short protocolUltra-short protocolMicrodose
Long protocol starting in the mid-luteal yieldsthe best IVF results*More oocytesMore pregnancies
* Daya S. (2008) Cochrane Database Syst Rev.
Antagonists
First used in large scale in 1995Competitive occupation of the GnRH
receptorNearly immediate profound suppression of
pituitary gonadotropinsSingle and multi-dose regimes existAlternative in luteal suppressive protocolsAllows for GnRH-agonist triggers
Antagonists
Concerns about need for LHAddressed with hMG or low dose hCG useConcerns about direct endometrial, oocyte, and
embryonic effectsChanges on expression on the endometrium at
the genomic level distinct from agonists
Less complexMore patient friendly
Copyright restrictions may apply.
Huirne, J.A. et al. Hum. Reprod. 2007 22:2805-2813; doi:10.1093/humrep/dem270
Variations in duration and initiation time of the GnRHantagonist in different GnRH antagonist protocols
Antagonists
Meta-analysis*Shorter stimulationLess Gonadotropins usedTrend toward less OHSSLess oocytesLess coordinated growthPregnancy rates???
*Al Inany, H and Aboulghar, M, (2006) Hum. Reprod.Kolibianakis, EM, (2006a) Hum. Reprod.
Antagonists
Meta-analysisThere is no significant difference in ongoing
pregnancy rates looking at the availablestudies which control of OCP suppression(n=4)Control for pt selectionControl for OCP pre-suppressionFixed Antagonist startN needed well greater than 100
Griesinger et al, (2008) Fertil Steril.
Which to use?
Agonist Antagonist
Egg DonorsYoung ovulatoryPCOSDim. ovarian reserve
Egg DonorsYoung ovulatoryHigh Risk for OHSSPCOSDim. Ovarian Reserve
Copyright restrictions may apply.
Huirne, J.A. et al. Hum. Reprod. 2007 22:2805-2813; doi:10.1093/humrep/dem270
Schematic overview of expected FSH and LHconcentrations in various GnRH analogue regimens
Copyright restrictions may apply.
Huirne, J.A. et al. Hum. Reprod. 2007 22:2805-2813; doi:10.1093/humrep/dem270
(a) Synchronized follicular developmentafter FSH administration in a long GnRH
agonist regimen
(b) Follicular development in a fixed day6 GnRH antagonist regimen without OC
pretreatment
Which to use
With GnRH-agonist a coordinated folliclepool is more likely.
With GnRH antagonist this may beachieved with OCP presuppression
The appropriated data to compare of GnRHagonist long protocol vs OCP+GnRHantagonist does not yet exist
Flexible GnRH antagonist versus GnRH agonistlong protocol in pts with PCOS treated for IVF
PCOS PatientsOCPs x 21 daysAgonist overlap 3 days with decrease with
gnd startrFSH Only 150 IU/dayTrigger with 5K hCGLuteal support with micronized progesterone
600mg/day
Lainas et al, (2009) Hum. Reprod.
Agonist vs Antagonist in PCOS pts RCT
N=220 Agonist‘n=110
Antagonist‘n=110
P-Value
Days of stim 12 10 0.001
FSH 1850 1575 0.019
E2 Concentration 2850 2144 0.004
Grade II OHSS (%) 60 40 <0.01
Ongoing PR (%) 50.9 47.3 .686
Lainas et al, (2009) Hum. Reprod.
Powered for lower pregnancy rateRCT hurdles >2800 pts needed to detect 5%
difference with PR of 35%Log regression for ongoing pregnancy# of prev attempts and BMI had p-values of < 0.05
Underpowered for PR conclusion butLess medsLess days of stimLess grade II ohss (overall 65.5 vs 45.5)
Agonist vs Antagonist in PCOS pts RCT
Lainas et al, (2009) Hum. Reprod.
Source: Fertility and Sterility 2010; 93:101-108 (DOI:10.1016/j.fertnstert.2008.09.048 )
Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions
Are gonadotropin-releasing hormone agonists losing popularity? Current trends at a largefertility center
Andrea Reh, M.D., Lewis Krey, Ph.D. and Nicole Noyes, M.D.
Trends in Lh-suppression protocol use from 1996-2005
57%~67%
Source: Fertility and Sterility 2010; 93:101-108 (DOI:10.1016/j.fertnstert.2008.09.048 )
Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions
Are gonadotropin-releasing hormone agonists losing popularity? Current trends ata large fertility center
Andrea Reh, M.D., Lewis Krey, Ph.D. and Nicole Noyes, M.D.
Clinical pregnancy rates (presence of FH/cycle start) per protocol
Which to use?
Agonist Antagonist
Age and DiagnosisOCP suppression vs luteal startMore shotsCost ?Longer stimulations
Longer lag to startMost experience
Age and DiagnosisOCP pre-supp. vs follicular start Less shots/patient friendlyCost Antagonist cost vs less days of stim
Easy to start Slow transition Fixed vs flexible start of antagonist
Outcomes? To be determined in your own clinic
t
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