Human ovarian follicular dynamics during natural menstrual cycles and oral contraception cycles
Baerwald, Angela Renee
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The objective of the research comprising this thesis was to characterize ovarian follicular development in healthy women of reproductive age undergoing natural menstrual cycles and oral contraception (DC) cycles. We quantified changes in the numbers and diameters of follicles, detected ovulation and assessed changes in the growth and regression of corpora lutea using high-resolution transvaginal ultrasonography. Changes in follicular and luteal development were then correlated with changes in concentrations of reproductively-active hormones and endometrial growth to provide a comprehensive approach to ovarian and uterine function. We documented, for the first time, that women exhibited waves of antral follicular development during the menstrual cycle. Two and three waves of follicle growth were observed. Major and minor waves of follicle development were characterized. Major waves were those in which a dominant follicle was selected for preferential growth; minor waves were those in which dominance was not manifest. Luteal progesterone production appeared to have a negative effect on the emergence and development of follicle waves in women. The ovarian follicular wave phenomenon has provided a new model for studying the growth and regression of ovarian follicles during the human menstrual cycle. Documentation of ovarian follicular waves in women has implications for the development of new strategies to manipulate ovarian follicular development, in particular hormonal contraceptive regimens and infertility therapies. We further documented that ovarian follicular development occurred during the compliant use of oral contraception. Follicles developed to ostensibly ovulatory diameters, and either regressed, ovulated or formed follicular cysts under the suppressive effects of DC. The majority of follicles that developed during DC use emerged during the hormone-free interval (HFI). We interpreted our findings to mean that ovarian follicular development during DC use was associated with loss of endocrine suppression during the HFI, rather than user non-compliance as previously speculated. The number and maximum diameter of follicles that developed during DC use were greater in women administered DC containing 20 µg versus 30-35 µg Ethinyl Estradiol formulations. Our results provided rationale for a reduction or complete elimination of the HFI in OC regimens, and the judicious use of low EE dose OC regimens (ie., 10 mm). Our findings demonstrated that dominant follicles secrete estradiol and become increasingly responsive to LH as they acquire functional dominance after becoming physiologically selected for preferential growth during the follicular phase of the menstrual cycle.