Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE) (fAMHOPE)

A Multicenter Prospective coHort Study of Controlled Ovarian Stimulation in Newly Diagnosed Breast Cancer PatiEnts (fAMHOPE)

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.

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasm Malignant Female
• Intervention / Treatment: Other: standard-stimulated cohort; Drug: Letrozole

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 1070
    • CUB-Hôpital Erasme
  • Brussel, Belgium, 1160
    • CHIREC- Hospital Delta
  • Liège, Belgium, 4000
    • CHC-Saint Vincent
• France
  • Lille, France, 59000
    • Centre Oscar Lambret
  • Lille, France, 59037
    • CHRU Lille
• Italy
  • Genova, Italy, 16132
    • Ospedale San Martino

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard-stimulated cohort; this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and wish to preserve their fertility by undergoing oocyte/embryo cryopreservation at the French participating centres.	Other: standard-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.; Other Names: COS
Experimental: letrozole-stimulated cohort; this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and wish to preserve their fertility by undergoing oocyte/embryo cryopreservation at the Belgian participating centres.	Drug: Letrozole; 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.; Other Names: Controlled Ovarian Stimulation (COS)
No Intervention: non-stimulated cohort; this cohort includes all newly diagnosed breast cancer patients who are candidates to receive (neo)adjuvant chemotherapy and who have access to the Fertility Clinics in all the participating centres but are not willing to preserve their fertility by undergoing oocyte/embryo cryopreservation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of the ovarian stimulation and oocyte collection procedure: Number of mature oocytes collected	Number of mature oocytes collected	an average of 2 weeks after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient with adverse events due to COS: OHSS	Adverse events reporting during COS (Ovarian Hyperstimulation syndrome-OHSS)	Through treatment procedure, an average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: total gonadotropin doses	Total gonadotropin doses (International Unit- IU)	An average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: duration of the COS	duration of the COS (days)	An average of 2 weeks after inclusion
Characteristics of Ovarian stimulation: type of stimulation	type of stimulation (standard or random-start).	An average of 2 weeks after inclusion
Efficacy of the ovarian stimulation and oocyte collection: Maturation rate	Maturation rate (number of total oocyte collected/number of mature oocytes)	An average of 2 weeks after inclusion
Outcomes of assisted reproductive technology procedures	Number of pregnancies and outcomes (premature delivery, miscarriage, abortion, delivery healthy babies, congenital malformation).	Through study completion, 5 years
Anticancer therapies effect on ovarian function: progesterone	Hormonal measurements Progesterone ng/ml	Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: AMH	Anti-Mullerian Hormone (AMH) measurements AMH ng/ml	Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: FSH	Follicle-Stimulating Hormone (FSH) measurements FSH IU/L	Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function: E2	Hormonal measurements E2 pg/ml	Inclusion, an average of 2 weeks, 6 months, 18 months, 30 months, 60 months
Anticancer therapies effect on ovarian function	Amenorrhea rate (6months without spontaneous menstruation)	An average 18 months, 30 months, 60 months after inclusion
Oncological outcomes 1	Invasive disease-free survival (iDFS)	5 years
Oncological outcomes 2	breast cancer-free interval (BCFI)	5 years
Oncological outcomes 3	overall survival (OS)	5 years
Circulating breast cancer cells level before stimulation	circulating tumor DNA (ctDNA)	Inclusion
Circulating breast cancer cells level after stimulation	circulating tumor DNA (ctDNA)	average of 2weeks after inclusion
Number of patient with adverse events due to egg collection	bleeding	An average of 2 weeks after inclusion
Number of patient with adverse events due to egg collection	pelvic infection	An average of 2 weeks after inclusion
Efficacy of the in vitro fertilization procedure: Fertilization rate	Fertilization rate (number of oocyte fertilized/number of embryo obtained)	Through study completion, 5 years

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Collaborators: University Hospital, Lille
• Investigators: Study Chair: Christine DECANTER, MD, CHRU Lille; Study Director: Isabelle Demeestere, MD, PhD, CUB-Hôpital Erasme; Study Chair: Matteo Lambertini, MD, PhD, ULB

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2019
• Primary Completion (Actual): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: February 26, 2020
• First Posted (Actual): February 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Fertility preservation; Letrozole; Ovarian stimulation
• Additional Relevant MeSH Terms: Neoplasms by Site; Skin Diseases; Breast Diseases; Neoplasms; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole
• Other Study ID Numbers: SRB_201808_163

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No