Stress and fertility

Please click through to the 2019 revision of this post at

https://biozhena.wordpress.com/stress-and-fertility-fertile-window-ovulation/

How stress affects the inherently narrow fertile window

Stress can do unwanted things to a woman and her menstrual cycle. In a nutshell, stress can make a woman completely infertile in this menstrual cycle (e.g., LPD, see below), or it can change the timing of her fertile window (the time of ovulation included) within the menstrual cycle. Any of this can cause problems and lead to more stress…

The medical term is stress response, and it refers to the overall reaction of the organism to any adverse stimulus, whether it be of physical, mental or emotional kind, internal or external. The purpose is to adapt to challenge, and this goes on all the time. (C’est la vie! Real life is a never-ending series of stress responses.) Should the compensating reaction of the organism be inadequate or inappropriate, a pathological disorder may result.

The HPA axis, the immune system and the sympathetic nervous system are involved in the stress response. Don’t get stressed by some undecipherable abbreviations or unknown words — look up The Alphabet of bioZhena, you may find it or them in there!

Just remember, this is no Alphabet of Ben Sira!

( /2007/11/28/the-alphabet-of-biozhena/)

Stress and the menstrual cycle

“It is a matter of conventional wisdom that perturbations in the external or internal environments – that is stress – can interfere with the normal course of the menstrual cycle.” To further quote the expert, “disturbances in the menstrual cycle occur in response to exercise and physical demands, stress and emotional demands, and diet and nutritional demands” [citation below, ref. 17].

As Michel J. Ferin writes, with reference to the brain component of the female reproductive control system, “with minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur, whereas with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency, anovulation, and amenorrhea may develop.”

A micro-glossary: The follicular maturation process is also called folliculogenesis. GnRH is a brain-produced hormone involved in folliculogenesis. A maturing follicle is a small, protective sac, gland, or cluster of cells in the ovary, in which an egg (ovum) develops towards ovulation, in order to have a chance to be fertilized.

 

 

And here is for you a baseline picture of how our folliculogenesis-in-vivo technique captures the course of folliculogenesis in baseline subjects (healthy and chemically clean i.e. no medication, less than 35 years old). Take your time to study the wealth of information particularly in the right-hand part of the image (use the linked slide):

 

 

For better legibility, click on the image. For more detail (presented in a PDF of 3 slides better viewed – incl. presenter notes – in Firefox, not in Chrome), go to:  https://biozhena.files.wordpress.com/2019/03/wealth-of-info-elucidation-silent-3-slides-animated-ed.pdf .  For the animation and narration of the first two slides, go to: https://biozhena.files.wordpress.com/2018/02/wealth-of-info-elucidation-3-animated-slides-2-narrated.pps (again, Firefox works while Chrome does not, at least here for me).

As for the scientific background of our work:  https://biozhena.files.wordpress.com/2007/12/what-is-stress.pdf is an ad hoc selection of a few abstracts from my files in (or before) 2007 on papers addressing ovulation, reproduction, folliculogenesis and stress. I referred to said area of biomedical science as psychoneuroimmunoendocrinology. Your perusal of the material with my markings (highlights) will help you understand the significance of the bioZhena technology for women’s healthcare and self-care. (The footer in the document shows obsolete email and physical addresses.)

Stress and the Ovulona^TM

As introduced above, our electrochemical sensor of the ectocervix, the Ovulona^TM, is a smart tissue biosensor for women’s reproductive self-help. It records menstrual cycle vital sign  signature data for OBGYN, PRIMARY CARE, RE and other healthcare providers’ use when needed.

Results obtained with our Ovulona prototypes lead to the conclusion that the technique appears to detect such phenomena as referred to by Dr. Ferin.

This is not merely the detected different rates of follicular maturation in different menstrual cycles, but even more significantly the delayed ovulations in those cycles where it takes longer than 1 day to reach the ovulation marker trough (minimum), as observed in some non-baseline subjects’ cyclic profiles. And the unprecedented  detection of the absence of dominant follicle maturation, which makes the woman infertile in the present menstrual cycle. Click on the composite image below for a better resolution of the contents.

Here (in the upper image) is the detection of Ferin’s “minimal reduction in (GnRH) pulse frequency, small undetected defects in the follicular maturation process may occur”.

Whereas (lower image), “with a higher degree of pulse inhibition the follicular phase may be prolonged, and luteal phase deficiency [LPD], anovulation, and amenorrhea may develop” – and, indeed, we have seen the LPD, the extended follicular phase and short luteal phase, and other aberrations in the cyclic profiles of different women over the years.

bioZhena’s technique is basically detecting non-pathological stress responses in menstrual cycles through monitoring cervical end-organ effects. Pathological stress responses are captured as well.

Abnormal cyclic patterns of the end-organ effects may serve as an early warning of pathological disorders. This remains to be systematically investigated. Anecdotal evidence in non-baseline cyclic profiles is compelling.

For a hint of how this came about, including samples of data from two pilot studies by independent investigators testing our prototypes, refer to these five  slides (they take a few moments to open; some browsers such as Firefox seem better for it): Five slides selected for bioZhena weblog

The five slides are as old as the text of the original blog post, so perhaps a recent more detailed explanatory illustration (clickable for better legibility) might be in order:

 

 

For better legibility of the contents and for links to the references, see the PDF of the slide shown in the image: https://biozhena.files.wordpress.com/2019/01/single-slide-ovulona-detects-delayed-ovulation-w.-links.pdf  (You can enlarge the contents using the browser zoom, or use the PPS slide show version of the slide (it takes a few moments to open): https://biozhena.files.wordpress.com/2019/01/single-slide-ovulona-detects-delayed-ovulation-w.-links.pps)

In general, the non-baseline cyclic profiles present certain quantitative deviations from baseline: e.g., their post-ovulation (luteal) phase can be not of the normal length of about 14 days (12 to 16) as in one of the illustrated cycles above. In such abnormal cycles with short luteal phases (<11 days, observed more often in older women), there is a lack of synchrony due to a mismatch between the ovarian steroids and the pituitary peptides [S.K. Smith et al., J. Reprod. Fert. 75:363, 1985].

Here is an example of a non-baseline cyclic profile of a woman with a short luteal phase (8 days); for comparison, the woman’s BBT profile in the same cycle is also shown:

A woman’s history of amenorrhea and/or of ovarian cysts is pertinent to the case of abnormally short luteal phase, but so is stress and its effect on the GnRH hormone generator in the hypothalamus of the brain, which affects the output of the pituitary peptides.

For example, it is known in a general way that norepinephrine and possibly epinephrine in the hypothalamus increase the GnRH pulse frequency. Conversely, the endogeneous opioid peptides, the enkephalins and beta-endorphin, reduce the frequency of the GnRH pulses. These interactions are particularly important at the time of the “mid-cycle” LH surge, affecting its timing and intensity [W.F. Ganong, Review of Medical Physiology, 17th edition, Appleton & Lange, 1995, Chapter 23].

The slow rate of descent of the Ovulona signal – seen in slides 1 and 2 of the 5 slides  above – descent from the short-term predictive peak to the ovulation marker trough (minimum) is a useful diagnostic feature that is indicative of an extended period of time required for the two “clocks” (the circhoral and the circamensual) to become synchronized as a precondition of ovulation.

Activation of the hypothalamus-pituitary-adrenal (HPA)-axis by physical, chemical, and psychological perturbations is known to result in elevated levels of serum corticosteroid hormones. Corticosteroids are the principal effectors in the stress response and are thought to be responsible for both adaptational and maladaptational response to perturbing situations. They have profound effects on mood and behavior, and affect neurochemical transmission and neuroendocrine control.

Cortisol, the predominant corticosteroid in primates, is often regarded as the “stress hormone” and consequently serves as a marker of stress. Cortisol can be measured in blood, urine, and saliva. For information about the adrenal gland and stress, go to http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/adrenal/index.html .

We logically mentioned stress in the post on Sub-fertility (or Reduced Fertility), in the following reminder. The endocrinologist professor Brown may be quoted:

“Failing to conceive when wanted is stressful and therefore favours infertility. It should be remembered that, apart from a few conditions such as blocked fallopian tubes, absent sperm and continued anovulation, most couples will conceive eventually without help. However, the modern expectation is one of immediate results, and the main function of assisted reproduction techniques is therefore to shorten the waiting time for conception.”

To which we would add that bioZhena aims to offer a more affordable and safer alternative to the A.R.T. approach. Besides offering to women’s healthcare providers the diagnostic technique with the capabilities outlined in the foregoing.

References as excerpted from our White Paper:

[17] Michel J. Ferin, “The menstrual cycle: An integrative view”, Chapter 6 in [2], pages 103 – 121.

[2] Eli Y. Adashi, John A. Rock, and Zev Rosenwaks, editors, “Reproductive Endocrinology, Surgery, and Technology”, Lippincott – Raven, 1996.

Terminology reminder:

Luteal phase is the phase after ovulation. Follicular phase is the phase before ovulation. Referencing the phases of the menstrual cycle. Amenorrhea = abnormal absence of menstrual bleeding. GnRH = gonadotropin releasing hormone. See The Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/