Hyperprolactinemia, Hypothalamic Amenorrhea, Infertility
Conditions
Brief summary
The purpose of this study is to develop a new protocol using two different types of fertility drugs that is more similar to the way the hormones act in a normal menstrual cycle (period). We are recruiting women who are trying to get pregnant through In Vitro Fertilization (IVF) who either have a high prolactin level (a hormone normally found in your blood that is produced in the brain) or have a condition known as hypothalamic amenorrhea in which one does not get regular periods due to low hormone levels. The ovaries can be stimulated with Follicle Stimulating Hormone (FSH) alone and with FSH and Luteinizing Hormone (LH). FSH causes eggs to be made while LH causes estrogen (hormone) production. The women in this study have low hormone levels and need both FSH and LH. Luveris® (LH hormone) is a new drug approved for egg production and is used in IVF. There is no set amount of LH nor a set protocol for LH use. Therefore, we are testing this new regimen. One group of women will receive a fixed dose of LH throughout their cycle while the other will decrease the dose of FSH while at the same time increasing the LH dose which is what happens in the natural menstrual cycle.
Interventions
DRUGLuveris fixed dose
Luveris 75IU daily throughout ovarian stimulation
DRUGLuveris increasing dose
Luveris 75IU until estradiol level reaches 250 pg/ml then increasing to 75IU BID for two days, then TID until hCG
Sponsors
EMD Serono
University Reproductive Associates
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 38 Years
Healthy volunteers
No
Inclusion criteria
1. 30 women under 38 years old at time of signing Informed Consent Form. 2. Evidence of hypothalamic amenorrhea (irregular menses and FSH and LH \<5 mIU/mL), uncorrected hyperprolactinemia (prolactin levels 10% above the upper limit of normal) or iatrogenic hypothalamic hypogonadism secondary to GnRHa suppression. 3. In good general health off of current medications which may confound response to study medications except GnRHa (Lupron Depot). 4. Desire to seek pregnancy actively during the study period. 5. A normal uterine cavity must have been confirmed by either hysteroscopy or hydrosonogram within two years of entering the study. 6. A semen analysis on the male partner deemed adequate for IVF by the attending physician within the past year or donor sperm available for insemination. 7. Only one treatment cycle per patient will be studied.
Exclusion criteria
1. uncorrected thyroid disease. 2. heart disease (New York Heart Association Class II or higher). 3. a history of, or suspected cervical, endometrial, or breast cancer. A normal Pap smear result within the last 24 months will be required. 4. enrolled into other studies that require medications, limit sex, or otherwise prevent compliance with the protocol at the same time. 5. to take other medications known to affect reproduction.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG. | 2 years |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Luveris Fixed Dose Participants in this arm will take Gonal F® and the same dose of Luveris® throughout the cycle. Their dose of Gonal F® will be adjusted throughout the cycle based on their response to the medication. The Luveris® dose will remain constant throughout.
Luveris fixed dose: Luveris 75IU daily throughout ovarian stimulation | 5 |
| Luveris Increasing Dose Patients assigned to this group will gradually reduce the Gonal F® dose while increasing the Luveris® dose during the cycle, which more closely mimics the natural menstrual cycle.
Luveris increasing dose: Luveris 75IU until estradiol level reaches 250 pg/ml then increasing to 75IU BID for two days, then TID until hCG | 9 |
| Total | 14 |
Baseline characteristics
| Characteristic | Luveris Fixed Dose | Luveris Increasing Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 14 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 9 |
| other Total, other adverse events | 0 / 5 | 0 / 9 |
| serious Total, serious adverse events | 0 / 5 | 0 / 9 |
Outcome results
Primary
The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG.
Time frame: 2 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Luveris Fixed Dose | The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG. | Large Follicles | 3 number of follicles |
| Luveris Fixed Dose | The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG. | Midsize Follicles | 4 number of follicles |
| Luveris Increasing Dose | The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG. | Large Follicles | 3 number of follicles |
| Luveris Increasing Dose | The Primary Outcome Will be Number of Large Follicles (16 mm or Greater in Diameter) and Midsize Follicles (Greater Than 12mm But Less Than 16mm) in Both Groups on the Day of Meeting Size Criteria for hCG. | Midsize Follicles | 4 number of follicles |