Human ovarian follicular dynamics during natural menstrual cycles and oral contraception cycles
Date
2003
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Doctoral
Abstract
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.
Description
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Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Obstetrics, Gynecology and Reproductive Sciences
Program
Obstetrics, Gynecology and Reproductive Sciences