Administration of Oral Contraceptives at Different Times of the Follicular Phase of the Menstrual Cycle
Condition: Contraception
Study type: Interventional

Summary: 
      We hypothesize that administration of OCs at varying follicular diameters will provide an
      appropriate model for the study of follicular atresia in women. Clinically, we hypothesize
      that the administration on OCs at different stages of the follicular phase will result in
      markedly different patterns of follicular development and/or atresia.
    

Detailed description: 
      This study is a single-centre, randomized, open-label, double-controlled protocol to study
      the patterns of ovarian follicular growth and regression in women administered 0.15mg
      desogestrel /0.03mg ethinyl estradiol at different stages of the follicular phase of the
      menstrual cycle.

      We tracked the growth and regression of dominant follicles after administration of OC by
      means of highly sophisticated transvaginal ultrasonography and computerized image analysis
      techniques. The extremely high resolution ultrasonography of the ovarian follicles and the
      computer-assisted image analysis are unique to the Women's Health Imaging Research Laboratory
      (WHIRL) at the University of Saskatchewan. The synergyne (© R.A. Pierson) image analysis
      program was developed in the WHIRL and has the ability to allow assessment of the physiologic
      status of follicles as small as 6 to 10 mm. This unique protocol will allow us to
      characterize patterns of follicular growth and atresia under the suppressive effects of oral
      contraception, as well as the assessment of anovulatory follicles which may develop when OCs
      are administered at advanced stages of follicular development.

      The working hypothesis is that the administration of monophasic OCs prior to and during the
      time of physiologic selection of the dominant follicle will prevent the development of an
      ovulatory follicle (selection occurs when the dominant follicle reaches 10mm [Baerwald &
      Pierson, unpublished data]). In addition, we hypothesize that administration of OCs after
      selection of the dominant follicle, at more advanced stages of follicular development will
      result in 1 of 4 scenarios: 1.) Ovulation of the dominant follicle, 2.) Regression of the
      dominant follicle, 3). Formation of a Hemorrhagic Anovulatory follicle (HAF) or Luteinized
      Unruptured Follicle (LUF), or 4.) Formation of a follicular cyst. We hypothesize that atresia
      of dominant follicles and formation of anovulatory follicular structures will be associated
      with limited endometrial development. In testing these hypotheses, we will determine if OCs
      can safely and effectively be administered at any time during the follicular phase of the
      menstrual cycle.

      This study will evaluate the ovarian and uterine responses to administration of a combined
      dose of 0.15mg desogestrel /0.03mg ethinyl estradiol at 1 of 3 different stages of the
      follicular phase of the menstrual cycle. The objectives of the trial are to:

        -  Develop new and more user-friendly administration schemes for OC use;

        -  Use the administration of OCs at different stages of follicular development in women as
           a model for studying follicular atresia;

        -  Assess the differences in kinetics, physiologic status (state of viability or atresia),
           and ultrasonographic image attributes of follicles which grow, regress, ovulate, or form
           anovulatory follicular structures after the administration of exogenous steroid
           hormones;

        -  Assess endometrial response to ovarian suppression by ultrasonographic evaluation of
           endometrial thickness and endometrial pattern.

      After screening measurements confirm subject eligibility, subjects will be randomized to
      initiate OC therapy at one of three different times of the menstrual cycle:

      Experimental Group #1: receives OCs when the dominant follicle reaches 10mm Experimental
      Group #2: receives OCs when the dominant follicle reaches 14mm Experimental Group #3:
      receives OCs when the dominant follicle reaches 18mm

      Fifteen women will be randomized to each of the 3 experimental groups in a stratified design
      scheme. Data collected from an ongoing OC trial (BMC# 2000-169) will serve as OC control data
      (n=15). Data collected from a previous study (BMC# 1988-80) will serve as natural cycle
      control data (n=60).
    

Intervention name(s): 0.15mg desogestrel /0.03mg ethinyl estradiol
Intervention type(s): Drug
Intervention MeSH terms: Ethinyl Estradiol; Desogestrel; Estradiol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: female contraception; oral contraceptive; emergency contraceptive; ovary; follicle; ovulation