1. Elonva in poor responders
Shahar Kol
August 2014

2. Who is a poor responder?
Human Reproduction 2011

3. Etiology? Depletion of ovarian follicle pool
Insufficient initial follicle number
Accelerated loss
Ovarian follicle dysfunction
Signaling defect
Enzyme deficiency
Autoimmunity

4. Risk factors Advanced maternal age Genetic conditions
Turner, FMR1, X deletions
Gene mutation: FSHR, LHR
Acquired conditions
Endomertioma
Chemo/radiotherapy
Ovarian surgery

5. Prediction of poor ovarian response (POR)
Broer et al, 2013

6. Which protocol?
Survey on POR from 196 centers in 45 countries, 124,700 cycles

7. 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

8. Adjuvant therapy Androgens (DHEA, testosterone, LH) Growth hormone
Co-enzyme Q10 supplementation
Other?

9. Significance of POR Poor prognosis for IVF success
Increased miscarriage risk
Early menopause

10. What is known about Elonva in poor responders?

11. 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 years

12. Number of oocytes Corifollitropin Alfa 150 µg rFSH 300 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
n = 675
11.0 (7.0)
n = 671
10.6 (6.7)
0.4 (–0.3 to 1.1)

13. Ongoing pregnancy rate
Corifollitropin Alfa
150 µg
rFSH
300 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)

14. Fertil Steril 2013

15. 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 IU/d
Polyzos et al. Fertil Steril 2013

17. 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

18. Retrospective pilot study.
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

21. Endocrine profiles during the follicular phase in women who are poor ovarian responders, according to age
E2, estradiol. *P for all comparisons between age groups at Days 2, 7, 9 and day of hCG triggering.

22. 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.

23. 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

27. The aim

28. 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.

30. Potential advantage of Elonva
In the natural follicular phase FSH decreases until the midcycle surge.

32. Flare effect Without using GnRH agonist No cysts formation, no LH rise
Robust recruitment of all available responsive follicles?

33. 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

34. 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.

35. 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