Official Title: “A Randomized, Open-Label Clinical Trial to Identify Predictive Factors for Controlled Ovarian Stimulation Using a Fixed Daily Dose of 200 IU Recombinant FSH in GnRH Antagonist Regimen With or Without Oral Contraceptive Scheduling”

Many couples suffer from infertility. When initial measures do not help, some couples require a process called in vitro fertilization (IVF). Each month, a woman produces at most one egg.

IVF helps these women make more than one egg per month. However, this involves taking hormones that stimulate the ovary to produce many (5-20) eggs at one time. The hormones are taken both by mouth and injected with a small needle. The eggs are removed from the ovary through a surgical procedure, then place in a dish for fertilization sperm to form an embryo.

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. Doctors choose a particular drug regimen called a protocol. Often times the drug protocol involves taking the birth control pill prior to starting the injectable medication. At this time, we are unsure if taking the birth control pill prior to starting the injectable medication helps, harms, or makes no difference in a person's chance at getting pregnant. This study will randomize (like flipping a coin) couples who are going to start IVF treatment into two groups. In one group the female partner will take oral contraceptive pills for 1 month prior to starting injectable medication, while the other group they will not take oral contraceptive pills prior to starting the injectable medication. We will then follow their progress to see how many eggs they produce and how many women get pregnant.

The purpose of this study is to identify if taking the birth control pill before starting the injectable medications for one month does or does not improve how the human ovary responds to the injectable medications. We currently do not know the answer to this question. The birth control pill is used commonly before in vitro fertilization (IVF) treatment cycles because it helps control the body's response to the injectable medication and prevents the ovary from becoming over-stimulated. It also assists in the timing of IVF treatment cycles.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment

Study Primary Completion Date: May 2008

Patients who have difficulty conceiving naturally often seek medical advice. These patients often undergo initial treatment with insemination using oral or injectable medication.

However, if this fails to achieve a pregnancy, patients often undergo in vitro fertilization (IVF). IVF is a process which involves a schedule of injectable medication to recruit several follicles, each containing an egg, to be retrieved under ultrasound guidance where they can then be fertilized. Embryos are then selected to be transferred back to the patient's uterus on day 3-5 following fertilization.

Women who ovulate begin to recruit the one egg they produce per month soon after their period begins. Therefore, the initiation of injectable medication should be on day 2 of a patient's menstrual cycle, prior to selection of the dominant follicle. If injectable medication is started after this point, only one egg will be produced. For patients who do not have regular cycles and for purposes of IVF scheduling, pretreatment with oral contraceptive pills (OCPs) is often used to reliable predict when injectable medication should be started. This is because following 1 month of oral contraceptive pills, women undergo a "withdrawal bleed" 1-3 days after discontinuation of the oral contraceptive pill; this is when the injectable medication is started. However, OCPs also suppress the patient's endogenous hormone secretion, an effect which may alter the patient's response to injectable medication, number of eggs retrieved, or pregnancy rate. Whether pre-treatment with OCP affects IVF outcome is not currently known.

Therefore, in patients who are scheduled to undergo treatment with IVF with a standard protocol, we would like to prospectively randomize them to OCP or no OCP pre-treatment. We would then place them on the same protocol of 200 IU of FSH with a medication to prevent the patients from ovulating prior to egg retrieval (Ganirelix). The identical stimulation protocol will be used for both groups to ensure that a difference in medication dose is not the cause of variation in IVF outcomes. In addition, the treatment of ovarian stimulation, egg retrieval, and embryo transfer is identical to non-study patients undergoing IVF.

Intervention(s) in this Clinical Trial

• Drug: Oral contraceptive pills (Desogen oral contraceptive)
  • Desogen oral contraceptive 1 tablet daily for 14 to 21 days
• Drug: no use of Desogen
  • Oral contraceptive pills not used prior to controlled ovarian stimulation

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 2
  • use of oral contraceptive pills prior to controlled ovarian stimulation
• Placebo Comparator: 1
  • no use of oral contraceptive pills prior to controlled ovarian stimulation

Primary Measures

• Total number of oocytes
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• Number of mature oocytes
  • Time Frame: 12 weeks
    Safety Issue?: No
• Number of follicles on stimulation day 8
  • Time Frame: 12 weeks
    Safety Issue?: No
• Number of follicles on day of hCG
  • Time Frame: 12 weeks
    Safety Issue?: No
• Number of fertilized (2PN) oocytes
  • Time Frame: 12 weeks
    Safety Issue?: No
• Number of good quality embryos
  • Time Frame: 12 weeks
    Safety Issue?: No
• Cycle cancellation rate
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

• Females of couples with an indication for IVF and/or ICSI scheduled for their first
• COS treatment cycle
• Females >18 and ≤39 years of age at the time of signing informed consent
• BMI ≤ 32 kg/m2
• Normal menstrual cycle length; 24-35 days
• Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed)
• Willing and able to sign informed consent

Exclusion Criteria:

• History of/or any current endocrine abnormality
• Less than 2 ovaries or any other ovarian abnormality (inc.>10mm endometrioma)
• Presence of unilateral or bilateral hydrosalpinx
• Presence of any clinically relevant pathology affecting the uterine cavity or fibroids
• ≥ 5cm
• History of recurrent miscarriage (3 or more, even when unexplained)
• FSH or LH > 12 IU/L as measured by a local laboratory (sample taken during the early follicular phase: menstrual day 2-5)
• Any clinically relevant abnormal laboratory value (FSH, LH, E2, P, total T, prolactin, TSH, blood biochemistry, hematology and urinalysis) based on a sample during the screening phase.
• Contraindications for the use of gonadotropins (tumors, pregnancy, lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts)
• Contraindications for the use of oral contraceptive pills (h/o thromboembolism, breast cancer, undiagnosed vaginal bleeding)
• Recent history of/or current epilepsy, HIV infection, diabetes, cardiovascular, gastrointestinal, hepatic, renal or pulmonary disease
• Abnormal karyotyping of the patient or her partner (if karyotyping is performed)
• History or presence of alcohol or drug abuse within 12 months of signing the consent
• Use of hormonal preparations within one month prior to randomization
• 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: 39 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Weill Medical College of Cornell University

Overall Clinical Trial Officials and Contacts

Zev Rosenwaks, M.D. Principal Investigator Weill Cornell Medical College  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00628641

Study ID Number: 142003

ClinicalTrials.gov Identifier: NCT00628641

Health Authority: United States: Institutional Review Board