DEPO-Trigger Trial: GnRH Agonist DEPOt TRIGGER for Final Oocyte Maturation

For breast cancer patients who are candidates to receive chemotherapy, concurrent use of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) can be offered as ovarian protection. A recent meta-analysis of individual patient data from the largest randomised clinical trials in women with early breast cancer indicated beneficial effects of GnRHa ovarian suppression in reducing POI risk and increasing post-chemotherapy pregnancy rates with no negative effect on patients' outcomes. However, it should not be considered as an alternative to cryopreservation strategies in fertility preservation. Because ovarian stimulation for oocyte cryopreservation is usually performed using a GnRH antagonist protocol and typically involves final oocyte maturation triggering with a GnRH agonist, the investigators designed this study to explore the feasibility of combining the final oocyte maturation trigger and the start of ovarian suppression. Replacement of the 0,2mg triptorelin trigger by a GnRH agonist depot has potential to provide this dual action. However, the protracted action of the GnRH agonist depot will result in prolonged stimulation of multiple corpora lutea, which will lead to enhanced production of steroids (estradiol and progesterone) and growth factors such as vascular endothelial growth factor. Consequently, GnRH agonist-induced stimulation of multiple corpora lutea is potentially unsafe in a patient with breast cancer because of the impact of estradiol and progesterone on breast tumour cells. In addition, VEGF may increase the risk of OHSS, which will lead to postponement of cancer treatment. Therefore, short-term cotreatment with GnRH antagonists is needed to induce rapid luteolysis. To demonstrate the safety of GnRH agonist depot triggering followed by daily GnRH antagonist luteolysis, this pilot study is set out to analyse the endocrine profile and ovarian morphology of this novel protocol. Patients will be randomized before start of stimulation to either DEPOT group (group A) or control group (group B), only after patient eligibility has been established and patient consent has been obtained.