SL ‘00

Antagonists in patients Antagonists in patients with previous poor with previous poor ovarian responseovarian response

Geoffrey H TrewGeoffrey H Trew

Consultant in Reproductive Medicine & Surgery, Hammersmith HospitalConsultant in Reproductive Medicine & Surgery, Hammersmith Hospital

Chief of Service, Imperial College NHS TrustChief of Service, Imperial College NHS Trust

LondonLondon

Poor responders……….Poor responders……….

DifficultDifficult

group for ;group for ;

• PatientsPatients

• StaffStaff

• ResultsResults

Definitions…….Definitions…….

• MainMain ; number of egg < 5, cancelled cycles ; number of egg < 5, cancelled cycles

But also a lot of American studies use ;But also a lot of American studies use ;• Raised FSH• Female age >40• AFC < 5• Endometriosis grade III or IV

VariationVariation

The greater the number of The greater the number of protocols there are - the protocols there are - the

poorer the evidence for any poorer the evidence for any particular one.....particular one.....

Evidence Based MedicineEvidence Based Medicine

• Archie CochraneArchie Cochrane• Do we need Do we need

evidence ?evidence ?• Why ? Why ? • What evidence do What evidence do

we have ?we have ?

The evidenceThe evidenceOr some of it ……Or some of it ……

Best outcome…………Best outcome…………

But….But….

There are other important There are other important outcomes as well ;outcomes as well ;

• Egg collectionEgg collection

• Embryo transferEmbryo transfer

Agonist v AntagonistAgonist v Antagonist

• Cancellation RatesCancellation Rates

• Previous agonist cycle cancelledPrevious agonist cycle cancelled

• New cycle – increased doseNew cycle – increased dose

• Randomised to either agonist or antagonist Randomised to either agonist or antagonist

Cancellation Rate on following Cancellation Rate on following cycle with poor responders cycle with poor responders

Brook…Trew, J Obstet & Gynecol, 2006

0

5

1015

20

25

30

3540

45

50

Antagonist Buserelin

%

9.4

47.5

P=0.011

A Prospective RCT of microdose leuprolide v ganirelix …… ……

• Pilot study - 48 ptsPilot study - 48 pts

• previous poor responseprevious poor response

• … … ganirelix appears to be as effective as the ganirelix appears to be as effective as the microdose protocol and microdose protocol and may be a superior may be a superior choice in terms of cost and conveniencechoice in terms of cost and convenience

Schmidt et al Fertil steril May 2005Schmidt et al Fertil steril May 2005

Antagonists in IVF poor responders – results of randomised trial

• Antagonist v standard long ; 60 pts Antagonist v standard long ; 60 pts

Antagonist groupAntagonist group ; ;

• less drugs less drugs P = 0.0001 P = 0.0001

• more eggs more eggs P = 0.02P = 0.02

• Fewer cycles cancelledFewer cycles cancelled

• PR 17% per ET v 7% per ETPR 17% per ET v 7% per ETMarci et al RBM Online Aug 2005Marci et al RBM Online Aug 2005

Flexible GnRH Antagonist v flare up GnRH Agonist in poor responders…a RCT

• 5 or less oocytes with dose = or > 300iu5 or less oocytes with dose = or > 300iu

• Antagonist (180pts) v flare agonist (90pts)Antagonist (180pts) v flare agonist (90pts)

• PR ; PR ; 12.212.2% v % v 4.44.4% % ( p<0.048)

Lainas…Kolibianakis, et al : Hum Reprod April 2008

Poor respondersPoor responders• Just about every different Just about every different

protocol triedprotocol tried• Different FSH dosesDifferent FSH doses• Different Agonist doses Different Agonist doses • Antagonists fixed / flexibleAntagonists fixed / flexible• Various additives inc LH Various additives inc LH

growth hormone etcgrowth hormone etc• ‘‘Soft’ / Natural protocolsSoft’ / Natural protocols• Still poor results!Still poor results!

What is your preferred ovarian What is your preferred ovarian stimulation regimestimulation regime for “poor for “poor

responders” ?responders” ?

• Clomifene/ gonadotrophinClomifene/ gonadotrophin 26%26%

• Ultrashort agonistUltrashort agonist 23%23%

• Short agonistShort agonist 30%30%

• Long agonistLong agonist 17%17%

• Antagonist 58%(Serono Symposia Mtg Athens Dec 2006)

What is your preferred ovarian What is your preferred ovarian stimulation stimulation dosedose for “poor responders” for “poor responders”

• 200 iu200 iu 2%2%

• 225 iu225 iu 4%4%

• 300 iu300 iu 21%21%

• 375 iu 375 iu 9%9%

• 450 iu 450 iu 47%47%

• > 450 iu> 450 iu 15%15%

What should the maximum FSH What should the maximum FSH dose be in poor respondersdose be in poor responders ? ?

• “ “ little or no clinical benefit in doses > 300 iu”little or no clinical benefit in doses > 300 iu”

• “…“…but costs and side effects were higher”but costs and side effects were higher”

Siristatidis & Hamilton, J Obstet Gynecol May 2007Siristatidis & Hamilton, J Obstet Gynecol May 2007

Other optionsOther options• Give up / expectant managementGive up / expectant management

• Corrective surgery of underlying problemCorrective surgery of underlying problem

• Natural cycle IVFNatural cycle IVF

• IUI - If no significant male factor / tubal factorIUI - If no significant male factor / tubal factor

• IUI and donor sperm if significant male factorIUI and donor sperm if significant male factor

• Egg DonationEgg Donation

• 50% + pregnancy rates50% + pregnancy rates

ConclusionsConclusions

• Difficult group to treatDifficult group to treat

• Poor pregnancy rates in true poor respondersPoor pregnancy rates in true poor responders

• Antagonist protocolsAntagonist protocols

• High dose of FSHHigh dose of FSH

PleasePlease ! !

• Do not use antagonists Do not use antagonists just just for poor for poor responders use them for responders use them for allall groups of groups of patients !!patients !!

• Results are good Results are good

• Patients love them !Patients love them !

Thank You !Thank You !g.trew@imperial.ac.ukg.trew@imperial.ac.uk