RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF
Condition: Breast Cancer; Infertility
MeSH terms: Breast Neoplasms; Infertility
Intervention: Letrozole; Letrozole
Intervention description: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level <150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level >350 pg/ml - 7.5 mg;; Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle
Intervention MeSH terms: Letrozole
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Female
Minimum age: 19 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: Letrozole; IVF (in vitro fertilization); Cryopreservation; Fertility Preservation; Breast Cancer

Summary:

      The purpose of this study is to compare two different ways to administer Letrozole to
      determine their effectiveness in blocking estrogen production during ovarian stimulation in
      patients with breast cancer prior to chemotherapy/radiotherapy so that oocytes or embryos can
      be cryopreserved and patients can possibly achieve a pregnancy after the treatment of breast
      cancer.

      During standard ovulation stimulation, the estrogen levels will exceed normal levels and may
      reach 10 times the normal level for a 2 week period. This may not be desirable in breast
      cancer patients. The study hopes to determine if the investigators can stimulate oocyte
      development in the conventional way and administer different doses of Letrozole as the
      oocytes develop, to keep estradiol levels low, increase the number of oocytes the
      investigators are able to recover, and improve the quality of those oocytes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female breast cancer patient with breast cancer diagnosis after surgery and before
             undergoing chemotherapy desiring fertility preservation with oocyte or embryo
             cryopreservation

          -  Healthy subject according to documented medical history and physical examination who
             has been diagnosed with breast cancer (estrogen and progesterone receptor positive
             and/or negative)

          -  Age less that 45 years at time of informed consent

          -  Verbal or written clearance from medical or surgical oncologist to undergo controlled
             ovarian hyperstimulation-IVF

          -  Delay to chemotherapy treatment will not jeopardize cancer treatment outcome

          -  Ovarian stimulation will not affect cancer treatment plan

          -  Transvaginal ultrasound scan (US) within one month of starting stimulation with no
             clinically significant pelvic mass

          -  Serum FSH level (Day 2-4) less than 25

          -  Negative pregnancy test prior to beginning Letrozole or gonadotropin therapy

          -  Willing and able to comply with the protocol

          -  Voluntary provision of written informed consent, prior to any study related procedure
             that was not part of normal medical care, with the understanding that the subject can
             withdraw consent at any time without prejudice to her future medical care

          -  Willingness to provide follow-up information on herself and babies born as part of
             this study

        Exclusion Criteria:

          -  Patients not medically cleared by their oncologist

          -  Patients with stage IV breast cancer based on the poor prognosis, general health of
             the patient, and higher uncertainty with delaying chemotherapy

          -  Any clinically relevant abnormal laboratory value (FSH >25 miu/ml, renal function,
             (greater than two times normal value), hepatic function (greater than two times normal
             value), blood biochemistry, hematology (elevated white blood count greater than 1.5
             times the normal value, hemoglobin <10mg/dL, thrombocytopenia), abnormal cholesterol
             profile (total cholesterol ≥ 300mg/dL, abnormal LDL greater than 2 times normal
             value,) based on a fasting sample during the screening phase

          -  Contraindications for the use of gonadotropins (i.e. Tumors other than breast cancer,
             pregnancy, lactation, undiagnosed vaginal bleeding)

          -  Recent or current medical conditions where the patient is not medically stable to
             undergo stimulation or egg retrieval, HIV infection, diabetes, cardiovascular disease,
             gastrointestinal, hepatic disease, undiagnosed pelvic mass, renal or pulmonary disease

          -  History or presence of alcohol or drug abuse within 12 months of signing consent

          -  History of severe allergic or anaphylactic reactions or hypersensitivity to any of the
             concomitant medication prescribed as part of the treatment regimen in this protocol

          -  Administration of investigational drugs within three months prior to signing the
             informed consent

          -  Use of insulin sensitizing agents at least one month prior to signing informed consent

          -  Any patient who is not a candidate for IVF