Risk of Infertility Related to Adjuvant Chemotherapy for Early Breast Cancer: Oocyte/Embryo Cryopreservation

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to perform a French multicenter prospective interventional study in order to assess the feasibility and safety of ovarian hyperstimulation for oocyte / embryo cryopreservation in young women with breast cancer. The oncologic and reproductive benefit / risk ratio will be investigated in the oncology and reproductive area.

Detailed Description
-----------------
Medical Oncology: Information and collection of consent, Imaging staging, Inclusion Physical examination Contraception advise given Reproductive medicine center: Ovarian reserve assessment: serum anti-mullerian hormone (AMH) measurement and antral follicle count (AFC) by ultrasound. Serology syphilis, hepatitis B and C, HIV (human immunodeficiency virus). In case of embryo cryopreservation, same serology determination for the men. Infertility risk and fertility preservation techniques information. In case of agreement, this technique will be done during the time-interval between surgery and chemotherapy Fertility preservation (COH stimulation, triggering and oocyte retrieval) Adjuvant chemotherapy: The chemotherapy regimen is 3 FEC (fluorouracil epirubicin cyclophosphamide) 100 followed by standard chemotherapy (according to local practice) +/- Trastuzumab. Adjuvant chemotherapy may only begin after the oocyte retrieval. Usual adjuvant chemotherapy is not changed During chemotherapy: Clinical exam before each cycle of chemotherapy AMH, AFC at cycle 6 After chemotherapy: Usual patient monitoring in expert center : physical examination at Month 3 (M3), M6 M9 M12 M18 and M24 and mammography at M9 then annual AMH at Month 3 (M3), M6 M9 M12 M18 and M24 AFC at Month 12 (M12) and M24

Official Title
-----------------
Risk of Infertility Related to Adjuvant Chemotherapy for Early Breast Cancer: Oocyte/Embryo Cryopreservation (CHACRY-1501)

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Procedure: Controlled ovarian hyperstimulation (COH)
* Procedure: Oocyte/embryo freezing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women with histologically proven breast cancer Aged 18 to 38 years old Planned adjuvant chemotherapy No prior chemotherapy Affiliated to a public health insurance program Informed consent signed by the patient Exclusion Criteria: Metastatic breast cancer Planned neo-adjuvant chemotherapy Hysterectomy Exclusive adjuvant hormonotherapy Positive serology for syphilis, hepatitis B or C, or VIH Contraindication related to use of r-FSH Pregnant or breastfeeding patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oocyte/embryo cryopreservation<br>Controlled ovarian hyperstimulation (COH) Oocyte/embryo freezing | Procedure: Controlled ovarian hyperstimulation (COH)<br>* After information and consent, patients are addressed to a reproductive medicine center. The COH will be performed according to a standardized protocol between surgery and the start of adjuvant chemotherapy. Follicular growth will be achieved with an antagonist protocol and by using high dose recombinant FSH (r-FSH). The triggering of the final follicular and oocyte maturation will be obtained by a GnRH (Gonadotropin Releasing Hormone) agonist injection in order to minimize the risk of ovarian hyper-stimulation.<br>Procedure: Oocyte/embryo freezing<br>* Egg or embryo freezing will be performed according to a standardized protocol: slow-freezing process for embryo; vitrification technique for oocytes. Cryopreserved oocytes and embryos will be stored in the biological bank of each reproductive medicine center (min. 10 years).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of oocytes: total number of oocytes preserved | The distribution of the total number of oocytes preserved will be summarized by the mean (standard error) and median (range) and presented with a 95% confidence interval. | after oocyte retrieval (35-36 hours after triptorelin injection) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of embryos: total number of embryos preserved |  | at 44-46 hours post intra-cell sperm injection | 
| Type of oocytes | mature, immature, fractured | after oocyte retrieval (35-36 hours after triptorelin injection) | 
| Toxicity related to the controlled ovarian stimulation according to NCI CTCAE v4.0 scale | Toxicities will be tabulated with frequencies and percentages by type of adverse events and by grade | 24 months | 
| Serum AMH measurement |  | baseline, at the end of the first sequence of chemotherapy, at the last injection of treatment, at Month 3, Month 6, Month 9, Month 12, Month 18 and Month 24 | 
| Antral Follicular Count (AFC) measurement |  | baseline, at month 3, at month 12, at month 24 | 
| Number of Spontaneous or medically assisted pregnancy(ies) | To measure the degree of project completion of subsequent pregnancy(ies) | up to 10 years after the end of the study or at 43 years old | 
| Rate of patients wishing for re-utilization of their frozen gametes | To assess the number of patients wishing for re-utilization of their frozen gametes | up to 10 years after the end of the study or at 43 years old | 
| Disease-free survival | defined as the interval between inclusion and the first occurrence of local, regional or distant relapse, estimated using the Kaplan-Meier method | through study completion, an average of 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
oocyte/embryo cryopreservation