Waves of Follicular Development Found in Human Menstrual Cycles
Menstrual Cycles

Richard J. Fehring
Reprint from Current Medical Research
Vol 15, No 1-2, Winter/Spring 2004
DDP/NFP, USCCB,
Washington, DC
Reproduced with Permission

Animal models (in particular the bovine estrous cycle) have been used to help understand the human menstrual cycle. During a cow's estrous cycle 2-3 waves of follicular development emerge throughout the cycle at regular intervals and are preceded by an increase of FSH. However, it is only the final wave of development that is ovulatory. Opposed to the wave theory of development is the theory that a single follicle grows by chance during a hormonally optimal period of the menstrual cycle. Based on the observation of ovarian follicular development during the luteal phase among women undergoing high-resolution transvaginal ultrasound, researchers from the University of Saskatchewan, Canada speculated that there might also be waves of follicular development in women as in animal models.1 To test the hypothesis that wave-like follicular development (i.e., changes in the number and diameter of follicles ) occurs in women, the Canadian researchers observed and described the daily growth and regression of ovarian follicles in women during an interovulatory interval (IOI). The IOI was defined as the interval from one ovulation to the next ovulation.

In order to test the follicular wave development theory, the researchers recruited 63 healthy women of reproductive age (average age 28 years and an age range of 19-43 years) to undergo daily "high resolution" transvaginal ultrasound. One ultrasonographer observed 90% of the cycles. Data from 13 of the 63 women participants were excluded due to what they called ovarian irregularities, e.g., 7 of the women developed an ovarian follicular cyst. They used two methods to characterize changes in follicular diameter; 1) the Identity Method in which they observed individual follicles of ≥ 8 mm throughout the IOI, and 2) the Non-Identity Method in which they sorted and counted the follicles of ≥ 4 mm in descending order of diameter. They identified the waves by defining the peaks and troughs of the graphed follicles. For example, "an increase and subsequent decrease in the number of follicles ≥ 5 mm, occurring in association with the growth of at least two follicles to ≥ 6 mm, was considered a "wave" of follicular development."


What the researchers observed was that 34 of the 50 women (68%) had two waves of follicular development and 16 (32%) had three waves of development. They also observed that the final wave of the cycle was ovulatory and the preceding waves were anovulatory in all 50 women. However, the diameter of ovulatory follicles grew smaller in 3-wave cycles as opposed to the 2-wave cycles. None of the 50 cycles observed had a single wave of follicular development.

The researchers indicated that their hypothesis that follicular development in women occurs in a wave-like fashion during the menstrual cycle was supported. They also stated that this challenges the previously held notion that a single cohort of antral follicles grows only during the follicular phase of the menstrual cycle. They postulated "the development of anovulatory follicles in the luteal phase occurs as a result of P-mediated inhibition of LH secretion to levels that allow follicular development to proceed to the antral or late antral stage, but do not allow the LH surge and ovulation to occur."

Comment

This article caused "waves of astonishment" among NFP users, teachers, and promoters around the world. Not because what was said in the article but rather what was reported about the article in the news and electronic media. Essentially the news media reported that women could ovulate more than once in a menstrual cycle and that NFP does not work. The news media based this erroneous notion on one speculative sentence in the study that mentioned, "it could, therefore, be speculated that follicles developing in the luteal phase of the cycle have the potential to ovulate in the presence of an LH surge" and by later remarks attributed to one of the authors, Dr. Roger Pierson (see below). There was no evidence (whatsoever) in this study that any of the 63 women had more than one ovulation or ovulated in the luteal phase, or had an ovulation other than LH-stimulated. The authors made no mention how their findings applied to NFP. Furthermore, as the authors stated, in order to ovulate you need to have an LH surge, and an LH surge does not happen when a woman is in the luteal phase because of the suppression of LH from the high levels of progesterone secreted by the corpus luteum. In interviews with the media one of the authors speculated on the use of NFP. For example, Dr. Roger Pierson stated in the Women's Health Matters Network web site (http://www.womenshealthmatters.ca/news) "up to 40 per cent of women may not be able to use natural family planning methods. That's because for women who experience two or three waves of dominant follicle growth per month there is no 'safe' time to have intercourse during the cycle—there may always be a follicle capable of ovulating." And he made a disparaging remark about NFP to the Canadian Broadcasting Corporation (CBC) "Dr. Pierson, the lead researcher on the study quipped, 'We have a word for people using natural family planning methods...parents.'" (http://www.cbc.ca/ stories/2003/07/08/ovulateO30708) These remarks are uncalled for and unprofessional.

The study itself is objective. It has a good theoretical base, clear definitions, and a well-documented method of identifying, classifying and tracking the follicles. This was only one study with a relatively small number of women participants who generated only a small number of cycles. It is interesting that although the women were healthy and in regular cycles, 13 of the cycles had ovarian irregularities. In the "methods" section of the study they stated that ultrasound scans were initiated 12 days after menses indicating that this would be before the first ovulation. I wonder if they missed any early ovulations. The study was hard to follow with regard to which follicles were induded in a count and which were tracked on a day-to-day basis. The "waves of follicular development" are not obvious in the figures provided in the article. I also wondered if they were biased towards what they previously had seen in animal models and in particular the bovine model. The model is also based purely on observations of follicles and not on the hormonal functioning of those follicles.

Although the wave model of follicular development is interesting and provides a different way of viewing the menstrual cycles and the role of the follicles, I did not find a lot new in the article. The fact that follicles develop as cohorts of 11-12 over several cycles is not new.2 Furthermore it is known that smaller antral follicles, produce only small amounts of estrogen and greater amounts of androgens.3 The larger antral follicles and in particular the mature graafian follicle secretes larger amounts of aromatase and estrogen. It is speculated that the differences in the secretion levels between the small and large follicles produces a balance of androgens and estrogens in the microenvironment of the ovary and may be instrumental in the selection of the dominant follicle and the regression of other smaller follicles.


Endnotes

1 Baerwald, AR., Adams, G.P., & Pierson, RA. A new model for ovanan follicular development during the human menstrual cycle. Fertility and Sterility. 2003;80:11~122. [Back]

2 Palter, S.F., & Olive, D.L. Reproductive physiology. Chapter in Novak's Gynecology (J.S. Berek Editor) 13th Edition; Philadelphia: Lippencott Williams & Wilkins, 2002. p. 165. [Back]

3 Carr, B.R. The normal menstrual cycle. Chapter in Textbook of Reproductive Medicine. (Edited by Carr, BR., & Blackwell, R.E.) Second Edition. Stamford, Connecticut: Appleton & Lange, 1997. p. 235. [Back]

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