ELONVA IN POOR RESPONDERS
SHAHAR KOL
AUGUST 2014
WHO IS A POOR RESPONDER?
Human Reproduction 2011
ETIOLOGY?
 Depletion of ovarian follicle pool
 Insufficient initial follicle number
 Accelerated loss
 Ovarian follicle dysfunction
 Signaling defect
 Enzyme deficiency
 Autoimmunity
RISK FACTORS
 Advanced maternal age
 Genetic conditions
 Turner, FMR1, X deletions
 Gene mutation: FSHR, LHR
 Acquired conditions
 Endomertioma
 Chemo/radiotherapy
 Ovarian surgery
PREDICTION OF POOR OVARIAN RESPONSE (POR)
Broer et al, 2013
WHICH PROTOCOL?
Survey on POR from 196 centers in 45 countries, 124,700 cycles
TREATMENT PROTOCOLS FOR POOR RESPONDERS
2010
 “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”.
ADJUVANT THERAPY
Androgens (DHEA, testosterone, LH)
Growth hormone
Co-enzyme Q10 supplementation
Other?
SIGNIFICANCE OF POR
Poor prognosis for IVF success
Increased miscarriage risk
Early menopause
• What is known about Elonva in poor responders?
ELONVA IN THE OLDER AGE GROUP
 Primary objective
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 attempt
Mean (SD)
Per oocyte pick-up
Mean (SD)
Corifollitropin Alfa
150 µg
rFSH
300 IU/day
n = 694
n = 696
10.7 (7.2)
10.3 (6.8)
n = 675
n = 671
11.0 (7.0)
10.6 (6.7)
Estimated
Difference
ANOVA (95% CI)
0.5 (–0.2 to 1.2)
0.4 (–0.3 to 1.1)
ONGOING PREGNANCY RATE
Per started cycle, %
(n/N)
Corifollitropin Alfa
150 µg
rFSH
300 IU/day
Estimated
Difference
(95% CI)
22.2
(154/694)
24.0
(167/696)
–1.9 (–6.1 to 2.3)
Fertil Steril 2013
OBJECTIVE:
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
CONCLUSION:
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
triggering.
CONCLUSION
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
Retrospective study
485 patients, 823 cycles
201<40 years, 284>40.
Gonadotropin daily dose ≥ 300 IU (FSH and/or hMG).
Polyzos et al , 2014
THE AIM
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.
FLARE EFFECT
Without using GnRH agonist
No cysts formation, no LH rise
Robust recruitment of all available
responsive follicles?
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.
IN CONCLUSION
 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.
Thank you