Recombinant LH, recombinant hCG and GnRH agonist to trigger
Transcript Recombinant LH, recombinant hCG and GnRH agonist to trigger
ELONVA IN POOR RESPONDERS
WHO IS A POOR RESPONDER?
Human Reproduction 2011
Depletion of ovarian follicle pool
Insufficient initial follicle number
Ovarian follicle dysfunction
Advanced maternal age
Turner, FMR1, X deletions
Gene mutation: FSHR, LHR
PREDICTION OF POOR OVARIAN RESPONSE (POR)
Broer et al, 2013
Survey on POR from 196 centers in 45 countries, 124,700 cycles
TREATMENT PROTOCOLS FOR POOR RESPONDERS
“There is insufficient evidence to
support the routine use of any
particular intervention either for
pituitary down regulation, ovarian
stimulation or adjuvant therapy in the
management of poor responders to
controlled ovarian stimulation in IVF”.
Androgens (DHEA, testosterone, LH)
Co-enzyme Q10 supplementation
SIGNIFICANCE OF POR
Poor prognosis for IVF success
Increased miscarriage risk
• What is known about Elonva in poor responders?
ELONVA IN THE OLDER AGE GROUP
To examine the efficacy and safety of a single
injection of corifollitropin alpha vs daily recombinant
FSH (rFSH) for controlled ovarian stimulation in
women aged 35-42 years
NUMBER OF OOCYTES
Per oocyte pick-up
n = 694
n = 696
n = 675
n = 671
ANOVA (95% CI)
0.5 (–0.2 to 1.2)
0.4 (–0.3 to 1.1)
ONGOING PREGNANCY RATE
Per started cycle, %
–1.9 (–6.1 to 2.3)
Fertil Steril 2013
To identify whether women with poor ovarian response
may benefit from treatment with corifollitropin alfa in a
GnRH antagonist protocol.
Design: Retrospective pilot study.
Intervention: Corifollitropin alfa (150 mg) followed by
300 IU rFSH in a GnRH antagonist protocol.
Comparative cohort: short agonist, hMG 300-450 IU/d
Polyzos et al. Fertil Steril 2013
Treatment of poor ovarian responders, as described
by the Bologna criteria, with corifollitropin alfa in a
GnRH antagonist protocol results in low pregnancy
rates, similarly to conventional stimulation with a
short agonist protocol.
Polyzos et al. Fertil Steril 2013
Will sequential administration of highly purified (hp)-HMG after
corifollitropin alfa in a GnRH antagonist protocol benefit women with
poor ovarian response according to the Bologna criteria?
Retrospective pilot study.
Polyzos et al, 2013
ENDOCRINE PROFILES DURING THE FOLLICULAR PHASE IN WOMEN WHO ARE
POOR OVARIAN RESPONDERS, ACCORDING TO AGE
E2, estradiol. *P . 0.05 for all comparisons between age groups at Days 2, 7, 9 and day of hCG
Corifollitropin alfa followed by hp-HMG in a GnRH
antagonist protocol results in very promising
pregnancy rates in young (<40 years old) poor
ovarian responders fulfilling the Bologna criteria.
RESULTS IN POR BY AGE
485 patients, 823 cycles
201<40 years, 284>40.
Gonadotropin daily dose ≥ 300 IU (FSH and/or hMG).
Polyzos et al , 2014
FOLLICULAR RECRUITMENT IS A RANDOM EVENT
Recruitment occurs all the time.
This explains our ability to start stimulation in luteal phase.
The number of recruitable follicles in any given time point
changes by chance.
The specific type of gonadotropins plays a secondary role.
POTENTIAL ADVANTAGE OF ELONVA
In the natural follicular phase FSH
decreases until the midcycle surge.
Without using GnRH agonist
No cysts formation, no LH rise
Robust recruitment of all available
Does the different pharmacokinetic Profile of
corifollitropin alfa result in a significantly higher
number of oocytes retrieved compared with rFSH?
Engage Study, Devroey et al , 2009
ELONVA: REDUCING TREATMENT BURDEN
POR patients are prone to have repeated IVF trials.
Reduced complexity and treatment burden
Sort treatment cycle (antagonist-based)
Fewer overall injections
Fewer injections per day
Fewer drop-out patients.
Elonva is an important addition to our fertility drugs arsenal.
the advantage of Elonva in the treatment of POR is yet to be defined by
randomized controlled studies, and by personal experience by each treating
physician in the field of ART.