By: Talia Caridi
Editor’s Note: Talia Caridi, DO, wrote this summary while taking the FACTS elective during her fourth year at Ohio University Heritage College of Osteopathic Medicine. She reviewed “Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings)” by James B. Brown, which describes ovarian activity as a continuum spanning anovulation through fully fertile ovulatory cycles across reproductive life. The research provides a physiologic foundation for fertility awareness-based methods (FABMs), highlighting how cervical mucus observations and urinary hormone monitoring offer insights into ovarian activity and fertility beyond bleeding patterns alone. To learn more about ovarian physiology, join us for our virtual conference on November 20th and 21st. The early bird deadline is October 15th, so register today to save up to $50.
Introduction
In his article, Brown identifies the continuous process of reproductive life transitions, from the absence of fertility in childhood to full fertility in adulthood and the loss of fertility at menopause. [1] Specifically, women progress through five types of ovarian activity: no ovarian activity, anovulatory follicular activity with various estrogen levels, a luteinized unruptured follicle (LUF), ovulation without a sufficient luteal phase, and ovulation with a sufficient luteal phase. Only the final type is fully fertile and can create and sustain pregnancy. Thus, it is most appropriate to recognize the types of ovarian activity as a natural continuum like other bodily processes, rather than sharply delineated categories which are often incorrectly labeled as “abnormal.”
“Women progress through five types of ovarian activity: no ovarian activity, anovulatory follicular activity with various estrogen levels, a luteinized unruptured follicle (LUF), ovulation without a sufficient luteal phase, and ovulation with a sufficient luteal phase. Only the final type is fully fertile.”
Methods
In the 1950s through 1970s, research studies involving 24-hour urinary measurements of estrogen and progesterone metabolites ascertained ovarian activity. Researchers measured estriol—which is uniquely hydroxylated before conjugation and excretion—estrone, and pregnanediol levels. The Billings Ovulation Method, which uses cervical mucus to assess ovarian activity, guided five-year observation studies in menarchal and menopausal women whose cycles were irregular. Gonadotropin therapy containing FSH and LH capably induced each of the five reported ovarian activity types, and HCG induced ovulation. This review used the ovulatory estrogen peak as its reference point and defined ovarian activity type based on the pregnanediol level reached between the estrogen peak and menses.
Results
Longitudinal studies showed a gradual rise in estrone and estradiol leading up to puberty until bleeding began. Following menarche, pregnanediol levels slowly increased until a sufficient luteal phase was eventually achieved—with a wide variability in time to reproductive maturity among individuals. Additionally, an identical progression along this ovarian continuum was identified amongst postpartum women starting with amenorrhea and moving towards fully fertile ovulatory cycles. Notably, peri-menopausal women followed the reverse sequence of the pubertal and postpartum continuum. Ovulatory mechanisms failed before the cessation of follicular activity as estrogen and FSH/LH levels fluctuated inversely. It was also found that estrogen peaks led to mostly regular bleeding patterns even in anovulatory cycles throughout the reproductive life.
“Following menarche, pregnanediol levels slowly increased until a sufficient luteal phase was eventually achieved—with a wide variability in time to reproductive maturity among individuals.”
Discussion
Overall, Brown’s study clarifies and confirms the correct approach for clinicians to take when analyzing a woman’s ovarian activity: They should identify cycles as being along the “ovarian continuum.” Importantly, the review identifies stress as the main driver of fertility changes and found that removing stress restored fertility in most cases. Brown describes these fertility changes as a natural, evolutionary response that helps avoid pregnancy during high-demand times. Therefore, he concludes that the five types of ovarian activity in the continuum are not to be considered abnormal, but rather, natural and normal progressions based on one’s age, activity, and environment.
“The review identifies stress as the main driver of fertility changes and found that removing stress restored fertility in most cases. Brown describes these fertility changes as a natural, evolutionary response that helps avoid pregnancy during high-demand times.”
Notably, this review emphasizes the value of ovarian hormone monitoring in identifying various types of ovarian activity in ways that bleeding patterns cannot identify. In ovulatory cycles, as the corpus luteum degenerates, progesterone levels decrease leading to menstruation. Although anovulatory cycles may also have bleeding, these patterns are associated with estrogen levels rather than progesterone. In cycles with fluctuating estrogen levels, irregular and sometimes uncontrolled withdrawal bleeding occurs as estrogen levels fall due to a loss of hormonal estrogen support for the endometrium. In cycles with constant estrogen levels, breakthrough bleeding occurs due to endometrial growth beyond the bounds of its own blood supply such that the dilated vessels rupture. Thus, anovulatory cycle bleeding indicates estrogen production but is inconclusive about which type of ovarian activity occurred. Urinary monitoring of ovarian hormones is more advantageous in identifying ovarian activity type because it is easier and less stressful than daily blood draws for women.
“In cycles with fluctuating estrogen levels, irregular and sometimes uncontrolled withdrawal bleeding occurs as estrogen levels fall due to a loss of hormonal estrogen support for the endometrium.”
This monitoring can also explain why ovulation does not equate to fertility. The post-peak urinary pregnanediol values that were used to analyze ovarian activity type needed to exceed 3 mg/24 h for one to two days to consistently confer fertility. Without sufficient progesterone production, the luteal phase wasn’t robust or long enough to sustain pregnancy. Shockingly, a deficient luteal phase was found to be the most common cause of infertility, affecting up to one-third of total cycles.
In summary, the Brown review uniquely identifies five types of ovarian activity that act along a continuum and merge with one another, not necessarily following a particular order of progression. Urinary hormone measurements were found to be a reliable means of identifying if ovulation occurred in most women and could accurately distinguish periods of fertility from infertility when used in combination with cervical fluid observations in perimenarchal and perimenopausal women. Lastly, it clarifies why ovulation does not necessarily indicate fertility. The study’s generalizability to modern women is limited by its use of pre-published data as far back as the 1950s, but it raises the question of how urinary hormone levels and cervical mucus observations can help modern women better understand their health and fertility. Future research should examine more specifically how changes in post-peak pregnanediol levels delineate between various causes of infertility and anovulation, including PCOS, endometriosis, and hypothalamic amenorrhea.
“Urinary hormone measurements were found to be a reliable means of identifying if ovulation occurred in most women, and could accurately distinguish periods of fertility from infertility when used in combination with cervical fluid observations in perimenarchal and perimenopausal women.”
The FACTS elective teaches the importance of tracking the female cycle using natural or fertility awareness-based methods (FABMs) to identify the various stages of the ovarian continuum. Although pregnancy itself is the soundest proof of a fertile cycle, ovulation may also be indicated by the post-ovulatory progesterone rise as explained above. The Billings Ovulation Method explains the anti-estrogenic effect of progesterone that induces a transition from abundant cervical mucus to minimal mucus production. [2] By observing cervical mucus, women may identify either ovulation or the absence of ovulation as well as the duration of their luteal phase. Couples may then use this information to either achieve or avoid pregnancy according to their family-planning goals. Finally, for women with anovulatory cycles or other signs of infertility, further workup to identify the underlying cause is indicated.
REFERENCES
[1] Brown, J.B. (2011). Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings). Human Reproduction Update, 17(2), 141-158. http://humupd.oxfordjournals.org/content/17/2/141.full.pdf+html
[2] Odeblad, E. (1994). The discovery of different types of cervical mucus and the Billings Ovulation Method. Bulletin of the Natural Family Planning Council of Victoria, 21(3), 3-34.
ABOUT THE AUTHOR
Talia Caridi, DO, is a family medicine resident at Memorial Hospital of South Bend in Indiana. She earned her medical degree from Ohio University Heritage College of Osteopathic Medicine and completed her undergraduate education at the University of Notre Dame.Her clinical interests include obstetrics, fertility care, direct primary care, and osteopathic manipulative treatment. She is interested in providing comprehensive women’s healthcare through cooperative and restorative reproductive medicine (RRM). During medical school, she enrolled in the FACTS elective to learn the fundamentals of fertility awareness-based methods (FABMs) and connect with students and fertility care practitioners who share her passion for holistic women’s health.
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