Breast Neoplasms, Fertility
Conditions
Keywords
Fertility preservation, letrozole, Ovarian stimulation
Brief summary
The purpose of this study is to evaluate efficiency and safety of controlled ovarian stimulation (COS) associated with an aromatase inhibitor (letrozole) for fertility preservation in breast cancer patients.
Detailed description
Patients enrolled in this study undergo standard or random start ovarian stimulation with Gonadotropins using antagonist protocol before the beginning of chemotherapy. Ovulation is triggered in all patients with a GnRH agonist since amendment P2015/091 (Decapeptyl 0,2mg). At oocyte retrieval, aspirated follicular fluid is separated from the flush medium for hormonal assays, and oocytes are denuded for ICSI(Intra Cytoplasmic Sperm Injection) or vitrification. Cumulus cells are collected for subsequent analysis of oocyte quality gene expression. A. Primary objective of the study is to evaluate efficiency of letrozole associated ovarian stimulation for fertility preservation in breast cancer patients in terms of oocyte maturation rate. Patients' results for primary endpoint are prospectively compared to infertile patients undergoing COS without letrozole. B. Secondary objectives of the study aim to evaluate safety of the protocol: 1. Estradiol and progesterone levels at ovulation triggering, ovulation and during luteal phase after oocyte retrieval (days 3 and 8) 2. The risk of disease relapse will be assessed by long-term follow-up of these patients (up to 5 years) as well as an evaluation of circulating tumoral DNA before and after ovarian stimulation. 3. Finally obstetrical outcomes will also be recorded.
Interventions
DRUGLetrozole
Patients start ovarian stimulation protocol according to their menstrual cycle phase at enrollment (standard or random start). Ovarian stimulation includes gonadotropins administration in a GnRH antagonist protocol Standard Protocol: letrozole is orally administered 2 tablets per day (2,5mgx2/d) from cycle day 2 throughout the ovarian stimulation with gonadotropins protocol until ovulation triggering. GnRH antagonist is administered as soon as at least one follicle reaches 14 mm. Random start protocol: letrozole is administered throughout the stimulation together with gonadotropins and GnRH antagonist, until ovulation triggering. Oocytes are collected 36h after ovulation triggering. All patients receive GnRH antagonist after oocyte retrieval for 3-7 days or until chemotherapy starts, to induce luteolysis.
Sponsors
Erasme University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Breast cancer female patients of less than 41 years old * Addressed to fertility preservation Unit before starting chemotherapy
Exclusion criteria
* Metastatic breast cancer * Known premature ovarian failure * Basal FSH \> 20 IU(International Unit) * Surgical contra-indications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oocyte maturation rate | At oocyte collection (48 hours after last administration of letrozole, following COS protocol). | Following letrozole associated COS, oocytes are collected and evaluated for maturation rate (%). These results are prospectively compared to infertile patients undergoing similar COS (GnRH antagonist protocol) without letrozole. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Circulating tumoral DNA | At enrollment (before letrozole associated COS) and at oocyte retrieval (48 hours after last administration of letrozole, following COS protocol) | 3 EDTA (Ethylene Diamine Tetra-Acetic Acid) tubes are collected for plasma extraction. 1 EDTA tube is collected for whole blood. Circulating tumoral DNA will be assessed on plasma samples according to primary tumoral mutation screening. Whole blood will used as reference. |
| Comparison of breast cancer recurrence rate in patients who underwent letrozole associated COS with an oncological control group | 2 and 5 years after letrozole associated COS | Oncological follow-up for relapse risk assessment will be carried out at 2 and 5 years of follow-up by medical chart review. Local, contralateral and/or distant recurrence of the disease will be reported. These data will be compared to a control group matched for age and type of disease who were diagnosed with breast cancer during the same period but did not undergo letrozole associated COS for fertility preservation. |
| Ovarian reserve | At enrollment, 2 and 5 years after letrozole associated COS for fertility preservation | AMH (anti-mullerian hormone) and FSH (follicle stimulating hormone) are assessed on blood samples to evaluate the gonadotoxicity of chemotherapy. |
| Hormonal levels | during stimulation at ovulation trigger and oocyte retrieval and during luteal phase (days 3 and 8) | Estradiol and Progesterone levels are measured on serum samples to confirm the effect of COS associated with letrozole on hormonal levels |
| Neonatal outcomes: gestational age at birth | Through study completion: data collection at 2 and 5 years after letrozole associated COS | Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS): gestational age at birth. Preterm delivery is defined by birth \< 37 weeks gestation. |
| Neonatal outcomes: delivery procedure | Through study completion: data collection at 2 and 5 years after letrozole associated COS | Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS). Delivery procedure is defined as spontaneous, instrumental or cesarean section |
| Neonatal outcomes: birth weight | Through study completion: data collection at 2 and 5 years after letrozole associated COS | Neonatal outcomes will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS). Birth weight will be reported in grams. |
| Obstetrical outcome: malformation rate | Through study completion: data collection at 2 and 5 years after letrozole associated COS | Malformation will be evaluated in patients who conceive with a previously vitrified oocyte (following letrozole associated COS): malformation assessment during prenatal morphology ultrasound and/or at birth |
Countries
Belgium
Outcome results
None listed