Use of GnRH antagonists for IVF

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Presentation transcript:

Use of GnRH antagonists for IVF Dr. Hakan Özörnek EUROFERTIL IVF Center

Structures of GnRH-antagonists in comparison to native GnRH

Agonist - Initial Phase: Stimulation GnRH Agonist Increased secretion of LH/FSH

Chronic Administration agonist Blockade post receptor mechanisms Some loss of receptors

Antagonist: Immediate Suppression GnRH Antagonist Receptor blocked no micro aggregation No effect immediate decrease of LH (FSH)

Hormon levels days

Hormon levels days

Advantages of GnRH-antagonists no flare-up effect no withdrawl symptoms shorter stimulation reduced gonadotrophin consumption fast reversibility

Long Agonist vs Antagonist

Antagonist protocols

Timing of Antagonist Administration

Suggested protocol

Discontinuation of IVF therapy Treatment burden Length of treatment Side effects Burden of risk OHSS

Advantages of Antagonists No initial flare up Shorter treatment duration Less gonadotrophin consumption Less clinic attendances Lower risk of OHSS No hypooestrogenemic effects Weight gain, headache, hot flushes, mood changes, vomiting

Agonist Antagonist

Disadvantages of Antagonists Lower pregnancy rates ?

Normoresponder-Antagonist Tubal infertility - DIR Cycles CPR/ET Agonist 7712 37.8 Antagonist 1852 36.1 Engel, et al., 2006

Normoresponder-Antagonist Patient 36 113 HMG/FSH ampoules 35.6 24.3* E2 level 2549 1786* Nr of oocytes 12.6 9.2 Transferred embryos 2.7 2.6 PR/ET 27.3 21.2 OHSS rate 11.1 3.5* Olivennes, et al., 2000

Normoresponder-Antagonist Patients 109 226 Gonadotropin usage 1800 1350* Stimulation length 26 9* E2 level 1370 1090 Nr of oocytes 9.6 7.9 PR/ET 41.7 35.8 The European and Middle East Orgalutran Study Group, 2001

Duration of stimulation (PCOS) Grisinger G, RBM Online, 2006

Gonadotrophin consumption (poor) Grisinger G, RBM Online, 2006

Gonadotropin consumption (PCOS) Grisinger G, RBM Online, 2006

Gonadotrophin consumption Al-Inany HG, RBM Online, 2007

Cancelled cycles (poor)

Number of oocytes Al-Inany HG, RBM Online, 2007

Number of oocytes (PCOS) Grisinger G, RBM Online, 2006

Miscarriage rate Al-Inany HG, RBM Online, 2007

OHSS Al-Inany HG, RBM Online, 2007

OHSS In a Cochrane rewiev the relative odds of hospital admission for OHSS was reduced bye 54 % with antagonists compared with agonists. Kolibianakis EM, Human Reprod Update, 2006

Hiperresponder-Antagonist Lower E2 levels by antagonist cycles. Ovulation can be triggered by agonist instead of HCG.

Clinical pregnancy rate Al-Inany HG, RBM Online, 2007

Clinical pregnancy rate (PCOS) Grisinger G, RBM Online, 2006

Clinical pregnancy rate (Poor) Grisinger G, RBM Online, 2006

Live Birth Rate

Live birth rate(poor) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (PCOS) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (Gonadotropin type) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (protocol type) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (agonist type) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (antagonist protocol) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate (antagonist type) Kolibianakis EM, Human Reprod Update, 2006

Live birth rate Al-Inany HG, RBM Online, 2007

Live birth rate Al-Inany HG, RBM Online, 2007

Live birth rate Kolibianakis EM, Human Reprod Update, 2006

Live birth rate Kolibianakis EM, Human Reprod Update, 2006

Analog use in EUROFERTIL

Analog use in EUROFERTIL 2006-08 Agonist Antagonist Cycles 537 2033 Age 28.4 31.5* Mean oocytes 12.5 9.7* Transferred embryos 2.9 2.6 CPR/ET 43.7 45.0

CPR in antagonist cycles

Conclusions Compared with GnRH agonists, GnRH antagonists are associated with reduced treatment duration and reduced risk of ovarian hyperstimulation syndrome Use of GnRH antagonists avoids pituitary down-regulation, which is associated with hypo-estrogenic adverse events.

Conclusions Meta-analyses comparing GnRH agonists and antagonists have calculated almost identical odds ratios (0.82-0.86) for the probability of live birth, although the difference was statistically significant in one analysis and not in another. The difference is unlikely to be of clinical significance.

Take home message The patient’s experience of IVF can often be marred by treatment burden, exposure to risk and psychological distress. Ovarian stimulation with antagonists co-treatment can provide live birth rates comparable to those achieved with the standart long agonist protocol and has advantages in terms of tolerability and safety.