TO: Members of the NFP list
From: Richard J. Fehring
Re: Ovarian Follicular Development Article

1. I have recently attended two NFP conferences, i.e., the Diocesan Development Program for NFP in Phoenix and the American Academy of Fertility Care Professionals annual meeting in Toronto. I enjoyed both meetings and found both to be of personal and professional interest. However, since I was away at these meetings I was unable to review the recent Baerwald, A.R., Adams, G.P., & Pierson, R.A., A new model for ovarian follicular development during the human menstrual cycle. Fertility and Sterility. 2003;80:116-122. Some individuals attending the conferences asked my opinion about the article. The following are some of my insights and reflections. I do concur with the assessment of the article by Dr. Rafael Mikolajczyk and apologize for repetition.

2. First of all, for those who did not read the article, Baerwald and colleagues observed the ovaries of 50 healthy women with high resolution transvaginal ultrasound for one ovulation-to-ovulation interval. What they found is that there were waves of follicles developing rather than just a cohort of 11-12 follicles that eventually resulted in one mature follicle which ended in ovulation. In some women (32%) they observed 3 waves of follicular development and others (68%) 2 waves of development. Waves of development occurred in both the follicular and luteal phase of the cycle. However, it was only the final wave that ended in ovulation. The authors indicated that this provided evidence that women have similar waves of follicular development that are found in other animals and in particular the cow - i.e., the bovine model. Most of the waves of follicular development involved small antral follicles that were 8 mm or less in diameter.

3. I found their study to be objective; it has a good theoretical base, clear definitions, and well-documented method of identifying, classifying and tracking the follicles. However, this was only one study with a relatively small number of women participants and who generated only a small number of cycles. I did find it interesting that although the women were healthy and in "regular" cycles, that 13 of the 63 observed cycles had ovarian irregularities.

4. 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. Furthermore is known that smaller antral follicles produce only small amounts of estrogen and greater amounts of androgens. 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.

5. What caused all of the commotion were the comments from one of the authors (Dr. Roger Pierson) that were quoted in both print and electronic media. He said that that "up to 40% of women may not be able to use natural planning methods because there will not be a 'safe' time for intercourse. In such women who experience two or three follicle growths each month there may always be a follicle capable of ovulating." He also was quoted as saying that what do you call couples who use NFP .... "Parents." I found these statements to be unprofessional and unfounded. Others articles mentioned that the article provided evidence in up to 10 of the women ovulated more than once. I think they (the news media) were confusing (or equating) waves of development with actual ovulation and women with ovarian irregularities with cycles that have more than one ovulation. http://www.cbc.ca/stories/2003/07/08/ovulate030708

6. The news media based this erroneous notion on one speculative sentence in the study that stated "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 i.e., Roger Pierson. There was no evidence (what so ever) 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 to the applications of their findings 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.

7. You can find an earlier version of this study that was presented at the 58th annual meeting of the American Society for Reproductive Medicine and published in the journal Biology of Reproduction. In this report they provide hormonal measures from the 50 cycles - all of the plotted hormonal profiles appear to have normal curves. You can find a copy of the article at http://www.biolreprod.org/ - just use the search engine at this site and type in the author Baerwald A.

8. I did write to Dr. Roger Pierson to verify his remarks and to provide evidence for cycles that have more than one ovulation (outside of a 24 hour time interval). I also asked him how his remarks fit with evidence from efficacy and fecundity studies on NFP. It is fine to speculate ---- but to do so outside of the realm of good research is irresponsible.

I hope this is of help to some.

Richard J. Fehring
Professor
Marquette University

Richard,
May I post your comments to the NFP Discussion Board on Delphi? This topic was causing something of a stir over there when it first reported in the media. Many of the posters realized there was some sort of misrepresentation and commented they hoped that there would be some NFP professionals questioning or commenting on the report.
Betti Bjorken
NFP Instr. - Dio. of Allentown
co-mod. NFP Discussion Board

Betti:
You certainly may post my comments. I will let you know if I get a response from the authors. I suspect not. I think that Dr. Pierson made these claims about double ovulations, and NFP not working to get media exposure for his research program. It has nothing to do with good science (i.e., his claims). And even his and Dr. Baerwald's research needs to be replicated. One study provides evidence --- but good research requires replication. Even in their research study - they did not indicate any inter-rater observations of their follicular counts, follicular diameters, and follicular frequencies. I am not sure if I see any difference in cohorts of follicles developing over several cycles (which was already known) and waves of follicles seen in one cycle - viewed from ovulation to ovulation rather than from menses to menses. They also need to factor in the micro hormonal environment - and why there is follicular selection, dominance and maturation. The authors seem to play their hand when they indicate that their findings will have implications for IVF and new contraceptive developments.

You can calm the stir of the members of the NFP discussion board in that the Baerwld et al research study did not provide evidence for double ovulations nor that NFP does not or could not work.

You could also view the prepared comments from the Georgetown University Institute for Reproductive Health.
http://www.irh.org/news.html#canadianstudy

Richard J. Fehring
Professor
Marquette University

Richard,
Thanks for the info. I've been collecting links on this topic for the discussion board's website.

Pardon me if this is an ignorant question, but I'm not one of the medical/scientific types when it comes to NFP (my husband and I are both media producers who happen to teach NFP). Is what the researchers are seeing in these follicular waves related at all to what NFP users sometimes observe as "multiple peaks"/"false peaks"/"doubtful peaks" (depending on the methodology vocab), or is this something different?
Betti

Hi -
I just read your note on the NFP List to Richard Fehring asking for clarification on what "waves of follicular development" would translate to in NFP language.

Although I don't know how Dr. Fehring will respond, I can tell you that based on nearly a million hormonal assays done in Australia by Dr. James Brown, it's called LUFs (Luteinized Unruptured Follicles). It's a discovery that was made about 30 years ago.

A woman who charts would show patches of fertility not ending in Peak. Since ovulation can only occur once each cycle, the Billings Ovulation Method would not call it a double Peak - it would be doubtful Peak. A true Peak ends in ovulation (just as a luteal phase can only exist as a result of ovulation).

Let me know if you have any questions.

Sue Ek
Executive Director of Billings Ovulation Method Association - USA
www.boma-usa.org
www.woomb.org

Betti:
I don't think you can correlate "mucus patches", "double peaks", "doubtful peaks", or "multiple peaks" of self-observed cervical mucus observations with what the authors of the Baerwald article call waves of follicular development. The journal Biology of Reproduction article shows somewhat normal curves of serum estrogen levels from the 50 women participants. However, the 13 cycles from the 13 women who were not included in the final data had irregular ovarian cycles - 7 of whom had anovulatory follicular cysts - and another had a luteinized unruptured follicle. These cycles no doubt would show a lot of cervical mucus variations from large (estrogenic) diameter follicles.

Richard J. Fehring
Marquette University

Somebody please tell me what a follicular "wave" is.
Thanks!

Steve Koob

The waves were determined based on peak-to peak and trough-to-trough measures of developing follicles.

"Peak-to-peak and trough-to-trough intervals in the number of follicles greater than or equal to 5 mm were evaluated for each woman during the IOI (i.e., an interval from one ovulation to the next) to determine whether follicles grew in a wave-like fashion." p. 117

"A trough was defined as a data point immediately preceded by at least twodecreasing data points and immediately succeeded by at least two increasing data points." p. 117-118

"A peak was defined as the highest point between two troughs, preceded by an increasing trend and succeeded by a decreasing trend." p. 118

SO THE DEFINITION OF A WAVE IS:

"An increase and subsequent decrease in the number of follicles greater than or equal to 5 mm, occurring in association with the growth of at least two follicles greater than or equal to 6 mm, was considered a "wave" of follicular development."

AND

"Wave emergence was defined as the day on which the largest follicle of the wave was detected at 4-5 mm."

These definitions are not real easy to follow. When you look at the graphs they provide - it is apparent that the largest and most frequent number of follicles are during the follicular phase of the cycles. The three wave phenomenon is not real easy to visualize on the graphs.

I wish all on the list a Happy and Blessed 35th Anniversary of Humanae Vitae - July 25th 1968 to July 25th, 2003.

Richard J. Fehring
Marquette University