Breast Cancer Female
Conditions
Keywords
Fertility preservation, Reproductive Techniques, assisted, Ovulation Induction, Oocyte Retrieval, Cryopreservation
Brief summary
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.
Detailed 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.
Interventions
DRUGTriptorelin 3.75 MG Injection
Depot Group (Group A) will receive Triptorelin 3.75mg Depot form for final oocyte maturation.
PROCEDURETransvaginal oocyte retrieval
Patients in both groups will undergo a transvaginal oocyte retrieval after ovarian stimulation.
Daily Group (Group B) will receive Triptorelin 0.2mg Daily form for final oocyte maturation.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Universitair Ziekenhuis Brussel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be randomized before start of ovarian 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. Group A will receive the GnRH agonist Depot form for final oocyte maturation followed by daily GnRH antagonist injections for 1 week. Group B will receive the GnRH agonist daily form for final oocyte maturation. After one week the Depot form combined with daily GnRH antagonist injections for 7 days, will be administered in view of ovarian protection during chemotherapy. Blood analysis and ultrasounds will be organised on day 3, 5 and 7 after oocyte pick-up in both groups.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Age \<36y * BMI ≥ 18 and ≤ 35 kg/m² * Early stage breast cancer * Any hormone receptor status * Any HER status * Cryopreservation of oocytes and/or embryos * Oncologist's approval to participate to the DEPO-trigger trial * Signed informed consent form
Exclusion criteria
* Contra-indications for controlled ovarian stimulation or oocyte retrieval * Necessity of neo-adjuvant chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety profile with regard to the risk of OHSS: assessment of change in Luteinizing Hormone (LH) | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate LH (IU/L). In the assumption of safety LH levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Oestradiol (E2) | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate Oestradiol (ng/L). In the assumption of safety Oestradiol levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Progesteron | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate Progesteron (mcg/L). In the assumption of safety Progesteron levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Follicle Stimulating Hormone (FSH) | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate FSH (IU/L). In the assumption of safety FSH levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in ovarian volume | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A transvaginal ultrasound will be performed to measure the ovarian volume according to the formula 'length x width x height x 0.523' mm³. In the assumption of safety ovarian volume should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in hematocrit | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate hematocrit (%). In the assumption of safety hematocrit levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in hemoglobine | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate hemoglobine (g/dL). In the assumption of safety hemoglobine levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in White Blood cell Count | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate White Blood cell Count (X10³/mm³). In the assumption of safety White Blood cell Count should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Platelet Count | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate Platelet Count (X10³/mm³). In the assumption of safety Platelet Count should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in estimated glomerular filtration rate (eGFR) | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate eGFR (mL/min/1.73m²). In the assumption of safety eGFR levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Creatinine | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate Creatinine (mg/dL). In the assumption of safety creatinine levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in Albumin | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate Albumin (g/L). In the assumption of safety Albumin levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
| Safety profile with regard to the risk of OHSS: assessment of change in liver function (AST, ALT, Gamma-GT, bilirubine, LDH) | During one week after the transvaginal oocyte retrieval (on day 3, 5 and 7) | A blood sample will be taken to evaluate liver function (AST U/L, ALT U/L, Gamma-GT U/L, bilirubine mg/dL, LDH U/L). In the assumption of safety liver function levels should be similar to that in the control group and there should be no events of ovarian hyperstimulation syndrome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Metaphase II oocytes | Immediately after the procedure of the transvaginal oocyte retrieval | Evaluation of the number of Metaphase II oocytes between the Depot group and Daily group |
| Evaluation of climacteric symptoms | One week after the transvaginal oocyte retrieval (on day 7) | Assessment of MENQOL (The Menopause-Specific Quality of Life) Questionnaire |
| Number of cumulus-oocyte complexes | During the procedure of the transvaginal oocyte retrieval | Evaluation of the number of cumulus-oocyte complexes between the Depot Group and Daily Group |
Countries
Belgium
Contacts
Primary ContactMichel De Vos, MD PhD
Backup ContactElsie Nulens
Outcome results
None listed