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

U

Universitair Ziekenhuis Brussel

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Breast Cancer Female

Treatments

Drug: Triptorelin 3.75 MG Injection

Procedure: Transvaginal oocyte retrieval

Drug: Triptorelin Injection

Study type

Interventional

Funder types

Other

Identifiers

NCT04616729

2019DEPO-TRIGGER001

Details and patient eligibility

About

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.

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. Short-term cotreatment with GnRH antagonists is needed to induce rapid luteolysis (in view of prevention of ovarian hyperstimulation).

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.

Full description

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

30 participants in 2 patient groups

GnRH agonist Depot form

Experimental group

Description:

Ovarian stimulation will be performed using a fixed antagonist protocol with Follitropin Alfa (daily in the evening) and Ganirelix or Cetrorelix (daily in the morning). Selection of the daily gonadotropin dose will be based on ovarian reserve parameters (AMH and AFC) and BMI. Co-administration of 5 mg of letrozole daily (in the morning) commencing on the first day of gonadotropin administration and continuing throughout the ovarian stimulation will be performed as this reduces oestradiol concentrations. GnRH agonist Triptorelin 3.75 mg Depot form will be used for final oocyte maturation. Ganirelix/Cetrorelix 0.25mg daily (in the morning) will resume for 7 days from the evening of the day of oocyte retrieval onwards. Hormone analysis, analysis of haematology and biochemistry and a pelvic ultrasound scan will be done on days 3, 5 and 7 after oocyte retrieval.

Treatment:

Procedure: Transvaginal oocyte retrieval

Drug: Triptorelin 3.75 MG Injection

GnRH agonist Daily form

Active Comparator group

Description:

Ovarian stimulation will be performed using a fixed antagonist protocol with Follitropin Alfa (daily in the evening) and Ganirelix/Cetrorelix (daily in the morning). Selection of the daily gonadotropin dose will be based on ovarian reserve parameters (AMH and AFC) and BMI. Co-administration of 5 mg of letrozole daily (in the morning) commencing on the first day of gonadotropin administration and continuing throughout the ovarian stimulation will be performed as this reduces oestradiol concentrations. GnRH agonist Triptorelin 0.2 mg Daily form will be used for final oocyte maturation. Hormone analysis, analysis of haematology and biochemistry and a pelvic ultrasound scan will be done on days 3, 5 and 7 after oocyte retrieval. The first administration of Triptorelin 3.75mg depot will be scheduled on the first day of the menstrual cycle after oocyte retrieval. To prevent the flare-up produced by the GnRH agonist, daily doses of 0.25mg of Ganirelix/Cetrorelix will be given for seven days.

Treatment:

Procedure: Transvaginal oocyte retrieval

Drug: Triptorelin Injection

Trial contacts and locations

2

Loading...

Central trial contact

Michel De Vos, MD PhD; Elsie Nulens