Mono-ovulation mystery

The textbook pattern of E2 and FSH changes during the follicular cycle was missing a critical piece of information. New indirect evidence point out a possibility that E2 and FSH do not gradually respectively ascend and descent, but oscillate, which would explain mono-ovulation in the human. Based on this editorial, by Dozortsev, Pellicer and Diamond, 2021

If you are a reproductive medicine insider, you probably know that the question of mono-ovulation in the human remains a mystery, in spite of a textbook explanation. It bugged me too for years, how is that possible that not only female ovulates only one egg at the time, but the side of the next ovulation is completely random. It turns out the textbook graphs of E2 and FSH progress through the follicular phase were all missing a vital piece of information, which we found recently while reviewing the data from Mira Care and Inito Inc. 

Here is the current vision of reproductive hormones profiles during the follicular phase: 

Credit to Wikipedia

The current explanation expects us to believe that E2 produced by multiple follicles will suppress FSH precisely to the level when only one follicle can continue development. This is very hard to imagine. 

By reviewing data from Inito Inc and MiraCare, which produce devices for home monitoring of the ovarian cycle, we have noticed that urine metabolite of E2 (E3G) oscillates within a wide range and so does, we speculate, should FSH.  

Mira with logo

This suggests that FSH does not drop to any magic specific level, but instead its multiple oscillation cycles enable one follicle to synchronize the availability of FSH with its own needs to emerge as the only dominant follicle and ovulate.  In this manuscript, we describe this in more detail. In the manuscript, we postulate that the oscillations have a frequency of about 48 hours. But this was based on once-a-day sampling. A more granular sampling shows that the frequency may be as short as 12 hours and as long as 72. This is apparently determined by the unique hormonal activity of the follicles and will vary from cycle to cycle and even within the same cycle. But regardless of the oscillations profile their role and final outcome – selection of a single follicle would not change.  

Below is a graphical representation of what we believe the real follicular phase looks like:  

New paradigm

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