Breast Neoplasm Malignant Female
Conditions
Keywords
Fertility preservation, Letrozole, Ovarian stimulation
Brief summary
This is a multicenter hospital-based prospective cohort study conducted in institutions with known expertise in performing oocytes/embryo freezing for fertility preservation. The study aims at refining the understanding of the efficacy and safety of controlled ovarian stimulation with or without letrozole in young women with newly diagnosed breast cancer who are candidates to receive (neo)adjuvant chemotherapy.
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 Gonadotropin Releasing Hormone-GnRH agonist. After retrieval, oocytes are denuded and matured oocytes are subjected to fertilization before embryo freezing or direct vitrification. Primary objective is to evaluate the efficacy of performing a controlled ovarian stimulation with or without letrozole in young women with newly diagnosed breast cancer who are candidates to receive (neo)adjuvant chemotherapy in terms of mature oocytes collected.
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 (5mg/d) from cycle day 2-3 throughout the ovarian stimulation with gonadotropins protocol until ovulation triggering. Random start protocol: letrozole is administered throughout the stimulation together with gonadotropins. GnRH antagonist is administered at cycle day 7 or as soon as at least one follicle reaches 12-14 mm. Oocytes are collected 36h after ovulation triggering with GnRH agonist.
OTHERstandard-stimulated cohort
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: Gonadotrophins started from cycle day 2-3 throughout the ovarian stimulation until ovulation triggering. Random start protocol: Gonadotrophins started at any time of the cycle and throughout the stimulation. GnRH antagonist is administered at cycle day 7 or as soon as at least one follicle reaches 12-14 mm. Oocytes are collected 36h after ovulation triggering with GnRH agonist.
Sponsors
University Hospital, Lille
Erasme University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
3 groups: * 113 patients in the standard-stimulated cohort, * 113 patients in the letrozole-stimulated cohort, * 339 patients in the non-stimulated cohort.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of invasive non-metastatic breast cancer (i.e. stage I to III); * Breast cancer diagnosis ≥18 and ≤ 40 years; * No prior history of gonadotoxic treatments; * Fertility preservation counseling for fertility preservation; * Written inform consent; * FSH \< 20 UI/L and/or antra-follicular count ≥ 6 (follicles of 2-9 mm) and/or AMH ≥ 6 pmol (only applicable for patients who undergo controlled ovarian stimulation for embryo/oocyte cryopreservation).
Exclusion criteria
* Newly diagnosed stage IV breast cancer (i.e. de novo metastatic breast cancer); * Prior diagnosis of other malignancies before breast cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected | an average of 2 weeks after inclusion | Number of mature oocytes collected |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characteristics of Ovarian stimulation: total gonadotropin doses | An average of 2 weeks after inclusion | Total gonadotropin doses (International Unit- IU) |
| Characteristics of Ovarian stimulation: duration of the COS | An average of 2 weeks after inclusion | duration of the COS (days) |
| Characteristics of Ovarian stimulation: type of stimulation | An average of 2 weeks after inclusion | type of stimulation (standard or random-start). |
| Efficacy of the ovarian stimulation and oocyte collection: Maturation rate | An average of 2 weeks after inclusion | Maturation rate (number of total oocyte collected/number of mature oocytes) |
| Outcomes of assisted reproductive technology procedures | Through study completion, 5 years | Number of pregnancies and outcomes (premature delivery, miscarriage, abortion, delivery healthy babies, congenital malformation). |
| Anticancer therapies effect on ovarian function: progesterone | Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months | Hormonal measurements Progesterone ng/ml |
| Anticancer therapies effect on ovarian function: AMH | Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months | Anti-Mullerian Hormone (AMH) measurements AMH ng/ml |
| Anticancer therapies effect on ovarian function: FSH | Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months | Follicle-Stimulating Hormone (FSH) measurements FSH IU/L |
| Number of patient with adverse events due to COS: OHSS | Through treatment procedure, an average of 2 weeks after inclusion | Adverse events reporting during COS (Ovarian Hyperstimulation syndrome-OHSS) |
| Anticancer therapies effect on ovarian function | An average 18 months, 30 months, 60 months after inclusion | Amenorrhea rate (6months without spontaneous menstruation) |
| Oncological outcomes 1 | 5 years | Invasive disease-free survival (iDFS) |
| Oncological outcomes 2 | 5 years | breast cancer-free interval (BCFI) |
| Oncological outcomes 3 | 5 years | overall survival (OS) |
| Circulating breast cancer cells level before stimulation | Inclusion | circulating tumor DNA (ctDNA) |
| Circulating breast cancer cells level after stimulation | average of 2weeks after inclusion | circulating tumor DNA (ctDNA) |
| Number of patient with adverse events due to egg collection | An average of 2 weeks after inclusion | bleeding |
| Efficacy of the in vitro fertilization procedure: Fertilization rate | Through study completion, 5 years | Fertilization rate (number of oocyte fertilized/number of embryo obtained) |
| Anticancer therapies effect on ovarian function: E2 | Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months | Hormonal measurements E2 pg/ml |
Countries
Belgium, France, Italy
Outcome results
None listed