Oral Microdose Lupron Versus Luteal Estradiol Trial in Poor Responder In Vitro Fertilization (IVF) Patients (OMLET)
Hundreds of thousands of couples in the United States experience infertility each year. When initial measures do not help, some couples require a process called ovarian stimulation and in vitro fertilization (IVF). Usually, a woman produces at most one egg each month. Ovarian stimulation helps these women make more than one egg per month. However, this involves taking hormones that stimulate the ovary to produce many eggs at one time. The stimulatory hormones injected with a small needle. The eggs are removed from the ovary through a surgical procedure and then placed in a dish for fertilization by sperm to form embryos. The embryos are grown in the laboratory then replaced into the woman's uterus 3-5 days later.
The stimulation of the ovaries is important. Some patients undergo ovarian stimulation for IVF but do not respond to the treatment. This is a very difficult situation because even though several ovarian stimulation protocols have been used for poor responder patients, it is not clear which protocol works best. In fact, two of the most commonly used protocols have not been directly compared.
This study will randomize (like flipping a coin) couples with a history of low response who are going to start IVF treatment into two groups. In one group the female partner will use a protocol called "E2 patch/antagonist". These women will use an estrogen patch and injected antagonist for several days before starting injectable fertility medications. The other group will use a protocol called "OCP/microdose". This group of women will use oral contraceptive pills (OCPs) and small doses of lupron along with the other injectable fertility medications. We will then follow their progress to see how many eggs they produce and how many women get pregnant.
|Infertility||Drug: Oral contraceptive pill and microdose lupron Drug: E2 patch/antagonist||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Controlled Trial of Treatment Protocols to Optimize Outcomes in Poor Responder In Vitro Fertilization (IVF) Patients: E2 Patch/Antagonist Protocol Versus OCP/Microdose Lupron Protocol|
- Pregnancy rate [ Time Frame: 7 weeks gestation ]
- Cycle cancellation rate [ Time Frame: Cycle completion ]
- Peak estradiol level [ Time Frame: Cycle completion ]
- Ampules of gonadotropins required during ovarian stimulation [ Time Frame: Cycle completion ]
- Number of days of ovarian stimulation [ Time Frame: Cycle completion ]
- Number of oocytes retrieved [ Time Frame: Cycle completion ]
- Number of embryos transferred [ Time Frame: Cycle completion ]
- Number of embryos frozen [ Time Frame: Cycle completion ]
- Embryo grade [ Time Frame: Cycle completion ]
- Implantation rate [ Time Frame: 7 weeks gestation ]
- Miscarriage rate [ Time Frame: 20 weeks gestation ]
- Pregnancy outcome [ Time Frame: Following delivery ]
|Study Start Date:||January 2009|
|Study Completion Date:||January 2012|
|Primary Completion Date:||September 2010 (Final data collection date for primary outcome measure)|
Oral contraceptive pills/microdose lupron
Drug: Oral contraceptive pill and microdose lupron
Desogestrel/ethinyl estradiol tablets, 0.15 mg/0.03 mg, one tablet by mouth daily for 14 days Leuprolide acetate 40 µg by subcutaneous injection twice a day during ovarian stimulation (approximately 14 days)
Estradiol patch/gonadotropin-releasing hormone antagonist
Drug: E2 patch/antagonist
Estradiol transdermal system 0.1 mg/day (25 cm2 patch. Patch changed every other day x 3. Final patch left on for about 7 days. Total duration of therapy approximately 14 days.
Gonadotropin-releasing hormone antagonist 0.25 mg subcutaneously every other day for 3 total doses.
Patients who have difficulty conceiving naturally often seek medical advice. These patients often undergo initial treatment with insemination using oral or injectable medications. However, if this fails to achieve a pregnancy, patients often undergo in vitro fertilization (IVF). IVF is a process which involves a protocol of injectable medications to stimulate the ovary to produce several eggs at once. These eggs are retrieved under ultrasound guidance and fertilized in the laboratory. After 3-5 days of growth in the laboratory, the appropriate number of embryos is then transferred back to the patient's uterus.
Sometimes, patients who go through ovarian stimulation and IVF do not respond well. These patients have low estrogen levels, few eggs retrieved, and fewer embryos to transfer back to the uterus. Overall, they have lower pregnancy rates than other patients. It is not clear which medication protocol would give them the highest chance of pregnancy. Two protocols, one called the "E2/antagonist" protocol and the other called the "OCP/microdose" protocol, are routinely used in poor responder patients. But, they have never been prospectively compared so it is not possible to say whether one approach is better.
In order to determine which medication protocol results in more pregnancies, we propose to randomize poor responder patients who are scheduled to undergo treatment with IVF to one of these two protocols. These two protocols are already standard care in IVF centers around the world. Following randomization, the clinical care of study participants will be the same as all other IVF patients. Specifically, the adjustment of medication, egg retrieval, and embryo transfer procedures will be identical to non-study patients undergoing IVF.
HYPOTHESIS We hypothesize that the poor responder patients undergoing ovarian stimulation for IVF with the E2/antagonist protocol will have a higher pregnancy rate than those in the OCP/microdose group.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00826839
|United States, New York|
|The Ronald O. Perlman and Claudia Cohen Center for Reproductive Medicine at Weill Cornell Medical College|
|New York, New York, United States, 10021|
|Principal Investigator:||Zev Rosenwaks, M.D.||Weill Medical College of Cornell University|