3 Etiology? Depletion of ovarian follicle pool Insufficient initial follicle numberAccelerated lossOvarian follicle dysfunctionSignaling defectEnzyme deficiencyAutoimmunity
4 Risk factors Advanced maternal age Genetic conditions Turner, FMR1, X deletionsGene mutation: FSHR, LHRAcquired conditionsEndomertiomaChemo/radiotherapyOvarian 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
11 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 years
12 Number of oocytes Corifollitropin Alfa 150 µg rFSH 300 IU/day Estimated DifferenceANOVA (95% CI)Per attemptMean (SD)n = 69410.7 (7.2)n = 69610.3 (6.8)0.5 (–0.2 to 1.2)Per oocyte pick-upn = 67511.0 (7.0)n = 67110.6 (6.7)0.4 (–0.3 to 1.1)
13 Ongoing pregnancy rate Corifollitropin Alfa150 µgrFSH300 IU/dayEstimated Difference(95% CI)Per started cycle, % (n/N)22.2(154/694)24.0(167/696)–1.9 (–6.1 to 2.3)
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/dPolyzos 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 ageE2, estradiol. *P for all comparisons between age groups at Days 2, 7, 9 and day of hCG triggering.
22 ConclusionCorifollitropin 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
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.
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 burdenSort treatment cycle (antagonist-based)Fewer overall injectionsFewer injections per dayFewer drop-out patients.
35 In conclusionElonva 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