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