Mid-luteal Phase Synchronization of Ovarian Folliculogenesis in Women

Mid-luteal Phase Synchronization of Ovarian Folliculogenesis in Women Protocol: WHIRL-07-2971

We hypothesize that administration of an aromatase inhibitor (AI) and hormonal contraceptives (HC) in the mid-luteal phase of the menstrual cycle will result in atresia of the follicles in the extant wave and cause synchronous re-emergence of a new follicular wave. We anticipate that this will provide us with information to facilitate the development of a new method for ovarian synchronization; a safer, more effective ovulation induction therapy; a new method for emergency contraception; and a greater understanding of human folliculogenesis.

Study Overview

• Status: Completed
• Conditions: Ovarian Follicle
• Intervention / Treatment: Drug: Marvelon; Drug: Nuvaring; Drug: Letrozole

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. female volunteers of childbearing potential;
2. are first time users of OC or have discontinued OC at least 2 months prior to study entry;
3. age between 18 and 35 years old;
4. normal body mass index (18-30);
5. has signed consent form; and
6. is in good health as confirmed by medical history, physical examination

Exclusion Criteria:

1. a positive pregnancy test will automatically exclude the volunteer from participation in this study.
2. any contraindication for oral contraception use;
3. known hypersensitivity to Letrozole and co-administered medications;
4. irregular menstrual cycles;
5. ultrasonographic evidence of ovarian dysfunction, such as Polycystic Ovary Syndrome (PCOS);
6. history of pituitary tumor;
7. HIV, HBV, HCV infection;
8. vaginal infection;
9. abnormal ECG;
10. abnormal lab tests for blood profile, liver function and renal function;
11. uncontrolled diabetes and blood pressure;
12. pregnancy (suspected or diagnosed) or lactation;
13. history or suspicion of drug or alcohol abuse;
14. history of severe mental disorders;
15. participation in an investigational drug trial within the 30 days prior to selection;

16. exhibits a disorder that is a contraindication to steroid hormonal therapy, including, for example, the following conditions:

    • history of, or actual, thrombophlebitis or thromboembolic disorders.
    • history of, or actual, cerebrovascular disorders.
    • history of, or actual, myocardial infarction or coronary artery disease.
    • acute liver disease.
    • history of, or actual, benign or malignant liver tumors.
    • history of, or suspected, carcinoma of the breast.
    • known, or suspected, estrogen-dependent neoplasia.
    • undiagnosed abnormal vaginal bleeding.
    • any ocular lesion arising from ophthalmic vascular disease, such as partial or complete loss of vision or defect in visual field.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: Oral Contraceptive	Drug: Marvelon; oral contraceptive
Experimental: Contraceptive Ring	Drug: Nuvaring; contraceptive vaginal ring
Experimental: Aromatase Inhibitors	Drug: Letrozole; Aromatase Inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate differences in the mechanisms of atresia, initiation of a new synchronous follicular wave, interval to follicle wave emergence, interval to emergence of dominant follicle, interval to menstruation, and endometrial thickness/pattern.	24-28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate between treatment group differences in ultrasonographic image attributes of follicular structures that develop after administration of treatment.	ongoing

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Roger A Pierson, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: November 27, 2007
• First Submitted That Met QC Criteria: November 28, 2007
• First Posted (Estimate): November 29, 2007

Study Record Updates

• Last Update Posted (Estimate): April 22, 2010
• Last Update Submitted That Met QC Criteria: April 20, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: ovarian synchronization; folliculogenesis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Progestins; Letrozole; Desogestrel; NuvaRing
• Other Study ID Numbers: WHIRL-07-59