Elonva in poor responders
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Transcript of Elonva in poor responders
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 ageGenetic 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
“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”.
2010
ADJUVANT THERAPY
Androgens (DHEA, testosterone, LH)Growth hormoneCo-enzyme Q10 supplementation Other?
SIGNIFICANCE OF POR
Poor prognosis for IVF successIncreased miscarriage riskEarly menopause
• What is known about Elonva in poor responders?
ELONVA IN THE OLDER AGE GROUP
Primary objectiveTo 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
Corifollitropin Alfa 150 µg
rFSH300 IU/day
Estimated Difference
ANOVA (95% CI)
Per attempt
Mean (SD)
n = 694
10.7 (7.2)
n = 696
10.3 (6.8) 0.5 (–0.2 to 1.2)
Per oocyte pick-up
Mean (SD)
n = 675
11.0 (7.0)
n = 671
10.6 (6.7) 0.4 (–0.3 to 1.1)
NUMBER OF OOCYTES
ONGOING PREGNANCY RATE
Corifollitropin Alfa 150 µg
rFSH300 IU/day
Estimated Difference (95% CI)
Per started cycle, % (n/N)
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
Polyzos et al, 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.
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 study485 patients, 823 cycles201<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 agonistNo cysts formation, no LH riseRobust 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 burdenSort treatment cycle (antagonist-based)Fewer overall injectionsFewer injections per dayFewer 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