Posts Tagged ‘gestation’

What is the mechanism of stress and how does it affect reproduction. An update. And: Be a young mother!

May 28, 2012

Ovulona™-related published scientific findings by others about disruption of fertility, about PCOS or Poly Cystic Ovarian Syndrome, how stress suppresses ovulation, about the hypothalamic amenorrhea of stress and postpartum blues/depression, about a CRH placental clock which determines the length of gestation and the timing of parturition and delivery, and the role of CRH in premature labor. How old age affects folliculogenesis as a stressor. Even how acute stress may induce ovulation in women.

This is an update in May 2012 on scientific literature reviewed in biozhena.wordpress.com/2007/12/27/   For an easier read (as opposed to the excerpts from scientific papers) you may want to go to Stress and Your Fertility at http://natural-fertility-info.com/stress-and-your-fertility.html but Hethir’s article does not refer to the Ovulona™. It simply tells you that stress has a negative effect on your chances of getting pregnant.

Unlike in the 2007 blog post, in the present update I share the complete abstracts of publications (way further down), pointing out in the abstracts certain details by bold font highlighting. On occasion I also point out in bold italics after the given abstract how the paper relates to the bioZhena project and the Ovulona™ personal monitor.

But first, I offer summary comments on the relationship of given papers to the bioZhena project, along with some details excerpted from the abstracts. Search result item numbers are indicated – so you can correlate my summary with the full abstracts and references shown below (after the Alfons Mucha picture).

In March 2018 I am adding here for reference the links to the page on the Ovulona (as updated in 2017)

https://biozhena.wordpress.com/2007/12/11/the-ovulona/

and to the Home Page of bioZhena’s Weblog

https://biozhena.wordpress.com/home-page-of-biozhenas-weblog/

Now to the review of literature:

Item 16:

This paper is suggestive of the prospective diagnostically beneficial use of the Ovulona™ in the management of PCOS [Poly Cystic Ovarian Syndrome], expected to be possible due to PCOS-caused alteration of the cyclic profile (detected via the exocervix, as the cervix monitors the integrated effects of all the hormones).

… effect is mediated by the hypothalamus, as evidenced by similar LH release in response to exogenous GnRH. This may represent the physiological condition that underlies ovarian follicular cysts.

Item 22.-related:

By emphasizing the critical timing of stress, this paper points by implication at the importance of routine Ovulona monitoring of Folliculogenesis In Vivo™, particularly  for assisting women who have difficulty to conceive but also for those practicing natural birth control. In either case, detecting any delay of ovulation is crucial.

The effects of stress on reproduction depend on the critical timing of stress, the genetic predisposition to stress, and the type of stress. The effect of stress on reproduction is also influenced by the duration of the responses induced by various stressors. Prolonged or chronic stress usually results in inhibition of reproduction, while the effects of transient or acute stress in certain cases is stimulatory…

Item 43:

This paper is related to our finding of delayed ovulation in some of the experimental subjects of two pilot studies of Ovulona™ prototypes – an important and unique feature of the Ovulona monitor, considering our way of life, full as it is of stress and not only stress of the psychological kind.

… findings support the hypothesis that stress-like increments in plasma cortisol [= increasing amounts of cortisol in blood] interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges.

Item 67:

Again, the listed paper is related to the PCOS problem, as is the next publication.

A follicle becomes cystic when it fails to ovulate and persists on the ovary. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. Altered metabolite and hormone concentrations may influence follicle growth and cyst development.

You will see below, in the full abstracts of the papers, that the reported experiments could not be performed with human subjects, and the last two abstracts selected from the veterinary literature search state the following.

Item 101:

Imposition of an experimental stressor suppresses GnRH/LH pulse frequency and amplitude. It is not yet clear whether delays in the surge are caused by interruption of the oestradiol signal-reading phase, the signal transmission phase or GnRH surge release. [Note: oestradiol is British spelling of estradiol, the most predominant form of estrogen.]

Item 102:

Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. … Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility.

What follows now is an analogous summary of the subsequent search on human (as opposed to animal) female fertility and stress.

Reviewing the few full abstracts with references, below, is highly recommended.

Item 3:

… These effects are responsible for the “hypothalamic” amenorrhea of stress, which is observed in anxiety and depression, malnutrition, eating disorders and chronic excessive exercise, and the hypogonadism of the Cushing syndrome. … Reproductive corticotropin-releasing hormone is regulating [those] reproductive functions [that have] an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. … Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

Item 3.-related:

Acute stress may induce ovulation in women. … acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. … Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

Item related to the above:

The stress system has suppressive effects on female and male reproductive function. Corticotrophin-releasing hormone (CRH), the principal regulator of stress, has been identified in the female and male reproductive system. … It has been suggested that there is a “CRH placental clock” which determines the length of gestation and the timing of parturition and delivery. … animal studies to elucidate the role of CRH in… premature labor.

Two literature search results – whereby I consider old age to be a stressor – are noted (with only certain excerpts from the abstracts) at the end of the post, consistent with the previously proposed motto: Be a young mother!

Hints for why – WHY TO BE A YOUNG MOTHER (besides coping more easily with other stressors) – cited from said two papers:

#1. Impaired folliculogenesis and ovulation in older reproductive-age women.

#2. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. END OF QUOTE.

Literature search was initially performed as Related Articles for http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Link&LinkName=pubmed_pubmed&from_uid=10844239  = What is stress, and how does it affect reproduction?

Dobson H, Smith RF. Anim Reprod Sci. 2000 Jul 2;60-61:743-52. Review.

PMID: 10844239 [PubMed – indexed for MEDLINE] Related citations

Selecting articles more recent than 2000 (search result numbers indicated). Most of these articles – in the initial search – are reports about animal models. (The reported work is obviously also for the benefit of agribusiness – for its reproduction-dependent profitability.)

16.

An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle.

PMID: 12021048 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Biol Reprod. 2002 Jun;66(6):1689-95.

An alteration in the hypothalamic action of estradiol due to lack of progesterone exposure can cause follicular cysts in cattle.

Gümen A, Wiltbank MC.

Department of Dairy Science, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Abstract

Many mammals, including cattle, can develop ovarian follicular cysts, but the physiological mechanisms leading to this condition remain undefined. We hypothesized that follicular cysts can develop because estradiol will induce a GnRH/LH surge on one occasion but progesterone exposure is required before another GnRH/LH surge can be induced by estradiol. In experiment 1, 14 cows were synchronized with an intravaginal progesterone insert (IPI) for 7 days, and prostaglandin F(2alpha) was given on the day of IPI removal. Estradiol benzoate (EB; 5 mg i.m.) was given 3 days before IPI removal to induce atresia of follicles. Cows were given a second EB treatment 1 day after IPI removal to induce a GnRH/LH surge in the absence of an ovulatory follicle. All cows had an LH surge following the second EB treatment, and 10 of 14 cows developed a large-follicle anovulatory condition (LFAC) that resembled follicular cysts. These LFAC cows were given a third EB treatment 15 days later, and none of the cows had an LH surge or ovulation. Cows were then either not treated (control, n = 5) or treated for 7 days with an IPI (n = 5) starting 7 days after the third EB injection. Cows were treated for a fourth time with 5 mg of EB 12 h after IPI removal. All IPI-treated, but no control, cows had an LH surge and ovulated in response to the estradiol challenge. In experiment 2, cows were induced to LFAC as in experiment 1 and were then randomly assigned to one of four treatments 1) IPI + EB, 2) IPI + GnRH (100 microg), 3) control + EB, and 4) control + GnRH. Control and IPI-treated cows had a similar LH surge and ovulation when treated with GnRH. In contrast, only IPI-treated cows had an LH surge following EB treatment. Thus, an initial GnRH/LH surge can be induced with high estradiol, but estradiol induction of a subsequent GnRH/LH surge requires exposure to progesterone. This effect is mediated by the hypothalamus, as evidenced by similar LH release in response to exogenous GnRH. This may represent the physiological condition that underlies ovarian follicular cysts.

This paper is suggestive of the prospective diagnostically beneficial use of the Ovulona™ in the management of PCOS [Poly Cystic Ovarian Syndrome] due to PCOS-caused distortion of the cyclic profile.

Sue Coe - Feed Lot, 1991, stone lithograph

Sue Coe – Feed Lot, 1991, stone lithograph
http://www.graphicwitness.org/coe/feedlot.jpg

22.-related (found as a related article of a related article)

Acta Vet Scand. 2008 Dec 10;50:48.

Stress and its influence on reproduction in pigs: a review.

Einarsson S, Brandt Y, Lundeheim N, Madej A.

PMID: 19077201 [PubMed – indexed for MEDLINE]

Free PMC Article

Division of Reproduction, Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7054, SE-75007 Uppsala, Sweden. stig.einarsson@kv.slu.se

Abstract

The manifestations of stress, defined as a biological response to an event that the individual perceives as a threat to its homeostasis, are commonly linked to enhanced activity of the hypothalamo-pituitary-adrenal (HPA) axis and the activation of the sympathetic adreno-medullary (SA) system. Activation of the HPA system results in the secretion of peptides from the hypothalamus, principally corticotropin releasing hormone (CRH), which stimulates the release of adrenocorticotropic hormone (ACTH) and beta-endorphin. ACTH induces the secretion of corticosteroids from the adrenal cortex, which can be seen in pigs exposed to acute physical and/or psychological stressors. The present paper is a review of studies on the influence of stressors on reproduction in pigs. The effects of stress on reproduction depend on the critical timing of stress, the genetic predisposition to stress, and the type of stress. The effect of stress on reproduction is also influenced by the duration of the responses induced by various stressors. Prolonged or chronic stress usually results in inhibition of reproduction, while the effects of transient or acute stress in certain cases is stimulatory (e.g. anoestrus), but in most cases is of impairment for reproduction. Most sensitive of the reproductive process are ovulation, expression of sexual behaviour and implantation of the embryo, since they are directly controlled by the neuroendocrine system.

This paper suggests the importance of routine monitoring of Folliculogenesis In Vivo™ for assisting women who have difficulty to conceive.

43.

Endocrine basis for disruptive effects of cortisol on preovulatory events.

PMID: 15625239 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Endocrinology. 2005 Apr;146(4):2107-15. Epub 2004 Dec 29.

Endocrine basis for disruptive effects of cortisol on preovulatory events.

Breen KM, Billings HJ, Wagenmaker ER, Wessinger EW, Karsch FJ.

Reproductive Sciences Program, University of Michigan, 300 North Ingalls Building, Room 1101 SW, Ann Arbor, Michigan 48109-0404, USA. breenk@umich.edu

Abstract

Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently inhibits gonadotropin secretion and disrupts ovarian cyclicity. Here we tested the hypothesis that stress-like concentrations of cortisol interfere with follicular phase endocrine events of the ewe by suppressing pulsatile LH secretion, which is essential for subsequent steps in the preovulatory sequence. Cortisol was infused during the early to midfollicular phase, elevating plasma cortisol concentrations to one third, one half, or the maximal value induced by isolation, a commonly used model of psychosocial stress. All cortisol treatments compromised at least some aspect of reproductive hormone secretion in follicular phase ewes. First, cortisol significantly suppressed LH pulse frequency by as much as 35%, thus attenuating the high frequency LH pulses typical of the preovulatory period. Second, cortisol interfered with timely generation of the follicular phase estradiol rise, either preventing it or delaying the estradiol peak by as much as 20 h. Third, cortisol delayed or blocked the preovulatory LH and FSH surges. Collectively, our findings support the hypothesis that stress-like increments in plasma cortisol interfere with the follicular phase by suppressing the development of high frequency LH pulses, which compromises timely expression of the preovulatory estradiol rise and LH and FSH surges. Moreover, the suppression of LH pulse frequency provides indirect evidence that cortisol acts centrally to suppress pulsatile GnRH secretion in follicular-phase ewes.

This paper is related to our finding of delayed ovulation in some of the experimental subjects of two pilot studies of Ovulona™ prototypes.

Steroids

67.

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.

Vanholder T, Opsomer G, de Kruif A.

Reprod Nutr Dev. 2006 Mar-Apr;46(2):105-19. Epub 2006 Apr 6. Review.

PMID: 16597418 [PubMed – indexed for MEDLINE]

Free Article

Related citations

Reprod Nutr Dev. 2006 Mar-Apr;46(2):105-19. Epub 2006 Apr 6.

Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.

Vanholder T, Opsomer G, de Kruif A.

Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.

Abstract

Cystic ovarian follicles (COF) are an important ovarian dysfunction and a major cause of reproductive failure in dairy cattle. Due to the complexity of the disorder and the heterogeneity of the clinical signs, a clear definition is lacking. A follicle becomes cystic when it fails to ovulate and persists on the ovary. Despite an abundance of literature on the subject, the exact pathogenesis of COF is unclear. It is generally accepted that disruption of the hypothalamo-pituitary-gonadal axis, by endogenous and/or exogenous factors, causes cyst formation. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant, which is attributed to insensitivity of the hypothalamus-pituitary to the positive feedback effect of oestrogens. In addition, several factors can influence GnRH/LH release at the hypothalamo-pituitary level. At the ovarian level, cellular and molecular changes in the growing follicle may contribute to anovulation and cyst formation, but studying follicular changes prior to cyst formation remains extremely difficult. Differences in receptor expression between COF and dominant follicles may be an indication of the pathways involved in cyst formation. The genotypic and phenotypic link of COF with milk yield may be attributed to negative energy balance and the associated metabolic and hormonal adaptations. Altered metabolite and hormone concentrations may influence follicle growth and cyst development, both at the level of the hypothalamus-pituitary and the ovarian level.

Again, the paper is related to the PCOS problem, as is the next publication.

67.-related (found as a related article)

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release. [J Reprod Dev. 2006]

J Reprod Dev. 2006 Feb;52(1):1-11.

Formation of follicular cysts in cattle and therapeutic effects of controlled internal drug release.

Todoroki J, Kaneko H.

Kimotsuki Livestock Hygiene Service Center, Kanoya, Kagoshima, Japan.

Abstract

Follicular cysts in cattle result from excessive growth of the dominant follicle without ovulation and still constitute a major reproductive disorder in this species. One key hormonal characteristic of cows with follicular cysts is the lack of an LH surge, although they have increased plasma estradiol concentrations. Another is a relatively high level of pulsatile secretion of LH that promotes continued growth of the dominant follicle. These LH characteristics seem to result from a functional abnormality in the feedback regulation of LH secretion by estradiol. Treatment with controlled internal drug release devices that increase circulating progesterone levels is effective in resolving follicular cystic conditions by 1) lowering pulsatile LH secretion and 2) restoring the ability of the hypothalamo-pituitary axis to generate an LH surge in response to an increase in circulating estradiol.

PMID: 16538030 [PubMed – indexed for MEDLINE]

Free full text

101.

Effects of stress on reproduction in ewes.

Dobson H, Fergani C, Routly JE, Smith RF.

Anim Reprod Sci. 2012 Feb;130(3-4):135-40. Epub 2012 Jan 26.

PMID: 22325927 [PubMed – in process]

Related citations

Anim Reprod Sci. 2012 Feb;130(3-4):135-40. Epub 2012 Jan 26.

Effects of stress on reproduction in ewes.

Dobson H, Fergani C, Routly JE, Smith RF.

School of Veterinary Science, University of Liverpool, Leahurst Campus, Neston, Wirral, United Kingdom. hdobson@liv.ac.uk

Abstract

Stressors, such as poor body condition, adverse temperatures or even common management procedures (e.g., transport or shearing) suppress normal oestrus behaviour and reduce ewe fertility. All these events are co-ordinated by endocrine interactions, which are disrupted in stressful situations. This disruption is usually temporary in adult ewes, so that, when prevailing conditions improve, normal fertility would resume. Imposition of an experimental stressor (shearing, transport, isolation from other sheep, injection of endotoxin or insulin or cortisol infusion) suppresses GnRH/LH pulse frequency and amplitude. Part of the cause is at the pituitary, but effects on GnRH/LH pulse frequency and the GnRH/LH surge are mediated via the hypothalamus. It is not yet clear whether delays in the surge are caused by interruption of the oestradiol signal-reading phase, the signal transmission phase or GnRH surge release. Stressors also delay the onset of behaviour, sometimes distancing this from the onset of the pre-ovulatory LH surge. This could have deleterious consequences for fertility.

CAPT. AJIT VADAKAYIL's two images of stressed out women

CAPT. AJIT VADAKAYIL’s two images of stressed out women
Via Google search on “stressed woman in modern art painting”
These two images are from Ship Captain Ajit Vadakayil
http://ajitvadakayil.blogspot.com/2011/02/modern-abstract-art-and-picasso-capt.html
Original sources:
Weeping Woman by Pablo Picasso (1937)
http://www.inminds.com/weeping-woman-picasso-1937.html
and
untitled file saved as AASHIK+1+001.jpg
http://4.bp.blogspot.com/-NijqSqXo2Tw/TVkVQkpCmII/AAAAAAAADcU/rzleByUNJfg/s1600/AASHIK+1+001.jpg

102.

Glucocorticoids, stress, and fertility.

Whirledge S, Cidlowski JA.

Minerva Endocrinol. 2010 Jun;35(2):109-25. Review.

PMID: 20595939 [PubMed – indexed for MEDLINE]

Related citations

Minerva Endocrinol. 2010 Jun;35(2):109-25.

Glucocorticoids, stress, and fertility.

Whirledge S, Cidlowski JA.

Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health/DHHS, Research Triangle Park, Durham, NC 27709, USA.

Abstract

Modifications of the hypothalamo-pituitary-adrenal axis and associated changes in circulating levels of glucocorticoids form a key component of the response of an organism to stressful challenges. Increased levels of glucocorticoids promote gluconeogenesis, mobilization of amino acids, and stimulation of fat breakdown to maintain circulating levels of glucose necessary to mount a stress response. In addition to profound changes in the physiology and function of multiple tissues, stress and elevated glucocorticoids can also inhibit reproduction, a logical effect for the survival of self. Precise levels of glucocorticoids are required for proper gonadal function; where the balance is disrupted, so is fertility. Glucocorticoids affect gonadal function at multiple levels in hypothalamo-pituitary-gonadal axis: 1) the hypothalamus (to decrease the synthesis and release of gonadotropin-releasing hormone [GnRH]); 2) the pituitary gland (to inhibit the synthesis and release of luteinizing hormone [LH] and follicle stimulating hormone [FSH]); 3) the testis/ovary (to modulate steroidogenesis and/or gametogenesis directly). Furthermore, maternal exposure to prenatal stress or exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal function and stress-related behaviors in offspring. Glucocorticoids are vital to many aspects of normal brain development, but fetal exposure to superabundant glucocorticoids can result in life-long effects on neuroendocrine function. This review focuses on the molecular mechanisms believed to mediate glucocorticoid inhibition of reproductive functions and the anatomical sites at which these effects take place.

At this point, let’s change the search tactics, by looking at Related Citations for this last one, which is clearly about human (as opposed to animal) female fertility and stress: http://www.ncbi.nlm.nih.gov/pubmed?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed&IdsFromResult=20595939

3.

Stress and the female reproductive system.

Kalantaridou SN, Makrigiannakis A, Zoumakis E, Chrousos GP.

J Reprod Immunol. 2004 Jun;62(1-2):61-8. Review.

PMID: 15288182 [PubMed – indexed for MEDLINE]

Related citations

J Reprod Immunol. 2004 Jun;62(1-2):61-8.

Stress and the female reproductive system.

Kalantaridou SN, Makrigiannakis A, Zoumakis E, Chrousos GP.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Ioannina, School of Medicine, Panepistimiou Avenue, 45500 Ioannina, Greece.

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis, when activated by stress, exerts an inhibitory effect on the female reproductive system. Corticotropin-releasing hormone (CRH) inhibits hypothalamic gonadotropin-releasing hormone (GnRH) secretion, and glucocorticoids inhibit pituitary luteinizing hormone and ovarian estrogen and progesterone secretion. These effects are responsible for the “hypothalamic” amenorrhea of stress, which is observed in anxiety and depression, malnutrition, eating disorders and chronic excessive exercise, and the hypogonadism of the Cushing syndrome. In addition, corticotropin-releasing hormone and its receptors have been identified in most female reproductive tissues, including the ovary, uterus, and placenta. Furthermore, corticotropin-releasing hormone is secreted in peripheral inflammatory sites where it exerts inflammatory actions. Reproductive corticotropin-releasing hormone is regulating [those] reproductive functions [that have] an inflammatory component, such as ovulation, luteolysis, decidualization, implantation, and early maternal tolerance. Placental CRH participates in the physiology of pregnancy and the onset of labor. Circulating placental CRH is responsible for the physiologic hypercortisolism of the latter half of pregnancy. Postpartum, this hypercortisolism is followed by a transient adrenal suppression, which may explain the blues/depression and increased autoimmune phenomena observed during this period.

3.-related (found as Cited by 7 PubMed Central articles)

Reprod Biol Endocrinol. 2010 May 26;8:53.

Acute stress may induce ovulation in women.

Tarín JJ, Hamatani T, Cano A.

Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences, University of Valencia, Burjassot, Valencia 46100, Spain. tarinjj@uv.es

Abstract

BACKGROUND:

This study aims to gather information either supporting or rejecting the hypothesis that acute stress may induce ovulation in women. The formulation of this hypothesis is based on 2 facts: 1) estrogen-primed postmenopausal or ovariectomized women display an adrenal-progesterone-induced ovulatory-like luteinizing hormone (LH) surge in response to exogenous adrenocorticotropic hormone (ACTH) administration; and 2) women display multiple follicular waves during an interovulatory interval, and likely during pregnancy and lactation. Thus, acute stress may induce ovulation in women displaying appropriate serum levels of estradiol and one or more follicles large enough to respond to a non-midcycle LH surge.

METHODS:

A literature search using the PubMed database was performed to identify articles up to January 2010 focusing mainly on women as well as on rats and rhesus monkeys as animal models of interaction between the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes.

RESULTS:

Whereas the HPA axis exhibits positive responses in practically all phases of the ovarian cycle, acute-stress-induced release of LH is found under relatively high plasma levels of estradiol. However, there are studies suggesting that several types of acute stress may exert different effects on pituitary LH release and the steroid environment may modulate in a different way (inhibiting or stimulating) the pattern of response of the HPG axis elicited by acute stressors.

CONCLUSION:

Women may be induced to ovulate at any point of the menstrual cycle or even during periods of amenorrhea associated with pregnancy and lactation if exposed to an appropriate acute stressor under a right estradiol environment.

PMID: 20504303 [PubMed – indexed for MEDLINE]

PMCID: PMC2890612

Free PMC Article

The above-related (found via their Ann N Y Acad Sci. 2006 Dec;1092:310-8 abstract titled “Reproductive” corticotropin-releasing hormone).

J Reprod Immunol. 2010 May;85(1):33-9.

Corticotropin-releasing hormone, stress and human reproduction: an update.

Kalantaridou SN, Zoumakis E, Makrigiannakis A, Lavasidis LG, Vrekoussis T, Chrousos GP.

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Ioannina Medical School, Ioannina, Greece. Sophia_Kalantaridou@hotmail.com

Abstract

The stress system has suppressive effects on female and male reproductive function. Corticotrophin-releasing hormone (CRH), the principal regulator of stress, has been identified in the female and male reproductive system. Reproductive CRH participates in various reproductive functions that have an inflammatory component, where it serves as an autocrine and paracrine modulator. These include ovarian and endometrial CRH, which may participate in the regulation of steroidogenesis and the inflammatory processes of the ovary (ovulation and luteolysis) and the endometrium (decidualization and blastocyst implantation) and placental CRH, which is secreted mostly during the latter half of pregnancy and is responsible for the onset of labor. It has been suggested that there is a “CRH placental clock” which determines the length of gestation and the timing of parturition and delivery. The potential use of CRH-antagonists is presently under intense investigation. CRH-R1 antagonists have been used in animal studies to elucidate the role of CRH in blastocyst implantation and invasion, early fetal immunotolerance and premature labor. The present review article focuses on the potential roles of CRH on the physiology and pathophysiology of reproduction and highlights its participation in crucial steps of pregnancy, such as implantation, fetal immune tolerance, parturition and fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis.

Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20412987 [PubMed – indexed for MEDLINE]

NOTA BENE or NOTE WELL: Chancy search result #1 (in our book, old age is a stressor):

J Clin Endocrinol Metab. 2003 Nov;88(11):5502-9.

Impaired folliculogenesis and ovulation in older reproductive aged women.

Santoro N et al.

… to test the hypothesis that older reproductive age [ORA >or= 45 yr old] women ovulate at a smaller follicle diameter and are more likely to produce multiple follicles during their menstrual cycle compared with mid-reproductive age [MRA 22-34 yr old] women. … ORA women were twice as likely to have multiple follicles as younger women. … grossly abnormal hormonal patterns were observed in some of the ORA women’s cycles. Other cycles demonstrated a failure of folliculogenesis. ORA women ovulated at a smaller mean follicle diameter … than younger women.

NOTA BENE or NOTE WELL: Chancy search result #2 (old age being a stressor):

J Obstet Gynaecol Can. 2011 Nov;33(11):1165-75.

Advanced reproductive age and fertility.

Reproductive Endocrinology and Infertility Committee; Family Physicians Advisory Committee; Maternal-Fetal Medicine Committee; Executive and Council of the Society of Obstetricians, Liu K, Case A.

Recommendations (excerpted from Abstract):

1. Women in their 20s and 30s should be counselled about the age-related risk of infertility when other reproductive health issues, such as sexual health or contraception, are addressed as part of their primary well-woman care. Reproductive-age women should be aware that natural fertility and assisted reproductive technology success (except with egg donation) is significantly lower for women in their late 30s and 40s.

2. Because of the decline in fertility and the increased time to conception that occurs after the age of 35, women > 35 years of age should be referred for infertility work-up after 6 months of trying to conceive.

5. Pregnancy rates for controlled ovarian hyperstimulation are low for women > 40 years of age.

6. The only effective treatment for ovarian aging is oocyte donation. A woman with decreased ovarian reserve should be offered oocyte donation as an option, as pregnancy rates associated with this treatment are significantly higher than those associated with controlled ovarian hyperstimulation or in vitro fertilization with a woman’s own eggs.

7. Women should be informed that the risk of spontaneous pregnancy loss and chromosomal abnormalities increases with age. Women should be counselled about and offered appropriate prenatal screening once pregnancy is established.

8. Pre-conception counselling regarding the risks of pregnancy with advanced maternal age, promotion of optimal health and weight, and screening for concurrent medical conditions such as hypertension and diabetes should be considered for women > age 40.

9. Advanced paternal age appears to be associated with an increased risk of spontaneous abortion and increased frequency of some autosomal dominant conditions, autism spectrum disorders, and schizophrenia. Men > age 40 and their partners should be counselled about these potential risks when they are seeking pregnancy, although the risks remain small.

Durer's Wife Agnes by Albrecht Durer, about 1494

Durer’s Wife Agnes by Albrecht Durer, about 1494
http://www.albrecht-durer.org/Durer%27s-Wife-Agnes.html

Although this literature search update is not necessarily complete, the blog post has grown long enough, so we better stop here. Enough food for thought for now… Don’t let all this stress you out! Just keep in mind: Be a young mother!

Oh, and do tell Uncle Rockefeller that Auntie Katharine (McCormick) made a little Big Mistake when she put her bets on chemistry and Cousin Margaret’s “magic pill”. Or is it the other Uncle that you are barbecuing with in Omaha, this Memorial Day?

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Saint Nicholas Day, his legend, and our modern day’s prematurity, EDD calculation, gestational age, problem with LMP

December 8, 2010

Could high prevalence of prematurity be a consequence of motherhood not being the top job held by society in high esteem? A modern paradox.

December 5 is the eve of St. Nicholas Day, the patron Saint of many people, cities and countries – including the largest one [ http://en.wikipedia.org/wiki/Saint_Nicholas#Deeds_and_miracles_attributed_to_Saint_Nicholas ]. St. Nicholas is remembered and celebrated in similar ways in some countries, rewarding well-behaved children but not the misbehaving ones… Which is why St. Nicholas, known as Svaty Mikulas, visits the children at home, in certain parts of Central Europe, in the evening along with an Angel and a Devil (Cert). The Saint asks the parents about the kids’ conduct…

Josef Lada_Mikulas, andel a cert

Josef Lada - Mikulas doma

Josef Lada – Mikulas doma

I share with you a depiction of the tradition drawn by Josef Lada in the troubled 1930s, an idyllic tradition of an industrial people, which they keep to this day…

Besides numerous miracles, this most popular of Saints was and is reputed for gift-giving (hence the commercialized Santa Claus transformation morphing St. Nicholas  with a Western or Northern European Father Christmas later on in the month of December).

There are numerous legends about Saint Nicholas’ miracles and his deeds of help. Perhaps the most famous one is about the three daughters of an impoverished man who could not afford a proper dowry for them, dowry being an ancient habit, the original purpose of which “was to provide ‘seed money’ or property for the establishment of a new household” – and we are now talking about the 300s CE [Christian Era].

The saint Bishop of Myrna saved the girls from the fate of slavery and prostitution by secretly dropping “three purses (one for each daughter) filled with gold coins through the window opening into the man’s house”, which gift made the young girls “eligible” again. It is also said that he dropped the gift down the chimney where stockings were hanging “over the embers to dry, and that the bag of gold fell into the stocking”. That’s beside the point because we are not discussing Santa of Christmas, but rather we are remembering St. Nicolas of December 6.

Jan_Steen_Het_Sint_Nicolaasfeest, The Feast of St. Nicholas

Jan_Steen_Het_Sint_Nicolaasfeest,                               The Feast of St. Nicholas

In those times many, many centuries ago, the chief purpose of young women’s life was motherhood, naturally within a marriage, hence the said dowry habit. In our times, many things have changed, including, unfortunately, young women’s attitude towards motherhood. Well, not just young women’s attitude…

Motherhood must be held in high esteem to reverse the trend reflected by an outcry in tweeter-sphere that’s a part of life nowadays: “I never felt marginalized as a woman until I became a mother”. Now this is very sad. Sad for society since the opposite should be the case.

Motherhood is the most important “job” in the world, and this is not some cute old-fashioned thought. Women bear enormous responsibility for the health of the nation, of humankind. Society should pamper them. Meaning: Society should be organized based on the recognition of Mother Nature’s design, which design – with the optimal years for motherhood in the early twenties – does not go away only because nowadays we can do all kinds of things – including octuplet pregnancies at grandmotherly age.

One consequence of the referenced changes is the currently common delays in getting married, and especially delays in bringing children into the world, starting a family. In other words, the unfortunate consequence is motherhood in later years of life than Nature intended. And then there are other consequences. Among them, prematurity.

Lou Beach, Preggers

Lou Beach, Preggers

@DrJenGunter not too long ago tweeted on prematurity, the most common cause of infant morbidity and mortality in the U.S.: “I just wrote a book on prematurity. Personal and professional experience”. See The Preemie Primer: A Complete Guide for Parents of Premature Babies–from Birth through the Toddler Years and Beyond [Paperback], Jennifer Gunter MD (Author) at http://www.amazon.com/Preemie-Primer-Complete-Premature-Babies/dp/0738213934/

Here is a citation [from http://www.preemieprimer.com/ ]:

My son Victor has dystonic cerebral palsy. He weighed 843 g at birth and had a grade 2 IVH. The bleed resolved in the NICU without hydrocephalus.

He is seven years old now. He is very stiff and is so shaky on a bicycle that we have given up trying for now. He couldn’t stand on one foot until he was 5. It took a very long time for him to get the hang of swimming and at the age of seven he is by no means a fish, but I feel if he were to fall in a pool he could keep his head above water. His digestive tract is very affected, but we have figured out ways to minimize these issues. It took countless hours of OT and thousands of hours of him practicing, but his writing is beautiful and God know where he gets his spelling ability from. He hopscotches like a pro. He is reading a grade level ahead. All without a CT scan or an MRI.

Based on his exam and his problem areas I am sure his cerebellum is a mess. In fact, I wonder if I would have pushed him so hard if I had seen a brain scan before we left the NICU?

“What we know about prematurity” is reviewed by the March of Dimes Campaign at http://www.marchofdimes.com/Mission/prematurity_indepth.html .

Today more than 1,400 babies in the United States (1 in 8 [= 12.5%]) will be born prematurely. Many will be too small and too sick to go home. Instead, they face weeks or even months in the newborn intensive care unit (NICU). These babies face an increased risk of serious medical complications and death; however, most, eventually, will go home. … In fact, the rate of premature birth increased by more than 20 percent between 1990 and 2006. … The rate fell to 12.3 percent in 2008 from 12.7 in 2007, a small but statistically significant decrease.

Why women deliver early? In nearly 40 percent of premature births, the cause is unknown. However, researchers have made some progress in learning the causes of prematurity. Studies suggest that there may be four main routes leading to spontaneous premature labor.”

Štyrský, Marriage

Štyrský, Marriage

Do refer to the referenced article for more about the four main causes:

  1. Infections and/or inflammation.
  2. Maternal or fetal stress.
  3. Bleeding.
  4. Stretching.

And then there is this: These four routes are not the only things to consider. Other factors, such as multiple pregnancy, inductions and cesarean sections, can also play a role. (Mostly man-made factors, we note. I say “mostly” because some multiple pregnancies happen also to women who did not get pregnant through the Artificial Reproductive Technologies… )

Prematurity is bad for infant, parents, and public health. We at bioZhena propose to contribute to the reduction of its prevalence, by making the FOLLICULOGENESIS IN VIVO™ [FIV™] technology available for routine use by women and their physicians. As a particular example, in relation to the referenced other factors, we propose to make it possible to compute the Expected Date of Delivery (EDD) based on the expectant mothers’ folliculogenesis data.

The idea is to get away from the gestation calculation popularized about 200 years ago in 1812 by a Dr. Naegele, for whom the 40 weeks or 10 lunar months rule of obstetrics is named. This rule of 280-day gestation assumes that the mother ovulates on day 14 of a 28 day menstrual cycle, which the readers of bioZhena’s Weblog know that it is an unrealistic assumption.

America in 1812, the time of Dr. Naegele’s 200 years of fame

America in 1812, the time of Dr. Naegele’s 200 years of fame

Napoleon & carabiniers_in_front_of_Moscow_1812

Napoleon & carabiniers_in_front_of_Moscow_1812

Allegedly*, it was Dr. Hermanni Boerhaave, in his time a highly respected academic physician, botanist and chemist, who read in the Bible that pregnancy should last 10 lunar months. He is said to have formulated – in the 1700s – a way of calculating the expected date of delivery (EDD).

Thus, expectant mothers get EDD today based on the myth of the baroque-era Boerhaave … Yet, already Aristotle taught that “the human fetus is expelled … at any period of pregnancy …; moreover, when the birth takes place in the eighth month, it is possible for the infant to live.”

The gist of the bioZhena hypothesis is this: The EDD can be projected quite well from ultrasonic measurements of the unborn baby’s head and body size, but for a more convenient, affordable and consequently more practical solution, we propose to seek a correlation between the Ovulona FIV™ attributes such as cycle length and the EDD/EDC. Importantly, this will be done by using the date of insemination, which will be easily – electronically – recorded by the user of the Ovulona™ as an integral part of the routine.

Trying to be fair or considerate to the women’s healthcare classics, I report an obgyn.net paper at http://www.obgyn.net/fetal-monitoring/fetal-monitoring.asp?page=cotm/9807/cotm_9807 . It is titled “’Back to the Future’ for Hermaani Boerhaave, or, ‘A rational way to generate ultrasound scan charts for estimating the date of delivery’” by Dr David J R Hutchon, Consultant Obstetrician, Memorial Hospital, Darlington, England. This is about the ultrasound approach, and he comments that: QUOTE “the approach mimics, in modern terms, the method originally formulated by Boerhaave. … If Boerhaave had had an ultrasound scanner, his paper might have read something like, ‘It is proved by numerous observations that 99 out of 100 births occur 22 weeks (at 18 weeks gestation) after the biparietal diameter of the fetus is 40mm’ (Fig 1).”

Besides his Figure 1, I also share Mr Hutchon’s (a British medical doctor, when Consultant, becomes Mr again) Fig. 2, “Regression analysis showing line fit plot. The number of days between scan and delivery has been converted to conventional gestation by subtracting from 280. The lower and upper dotted lines represent delivery at 42 and 37 weeks respectively.” QUOTE UNQUOTE.

Gestation age vs. crown rump length by DJR Hutchon

Gestation age vs. crown rump length by DJR Hutchon

Gestation vs. biparietal diameter by Hutchon

Gestation vs. biparietal diameter by Hutchon

Biparietal diameter is the (outer – inner) measurement of the fetal skull echo. Crown-rump length (CRL) is the measurement of the length of human embryos and fetuses from the top of the head (crown) to the bottom of the buttocks (rump). In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization. These are the Wikipedia reported definitions. The two weeks between 9 and 11 assume the “regular” length of the menstrual cycle, which is a theoretical assumption that could very likely be incorrect in practice, in the given woman and in the given last cycle of hers (because regularity is a myth, too). Well, look at the scatter in the data points, it’s telling.

In addition to the convenience, affordability and practicality of the bioZhena approach, do not overlook the feature that the data will be personal to the given woman, and the measurement will not refer to LMP. It will not rely on the woman’s recollection of her last menstrual period (instead, it will refer to the last electronically recorded intercourse); and it will not subject the baby to unnecessary ultrasound radiation.

For more on the topic, try under Gestation in the Alphabet of bioZhena https://biozhena.files.wordpress.com/2007/11/aaee-the-alphabet-of-biozhena.pdf (or https://biozhena.wordpress.com/2007/11/28/the-alphabet-of-biozhena/ ). See also the discussion under Parturition, where we express the expectation that parturition management will be revolutionized by the introduction of the Ovulona into obstetric and gynecological practice.

Anderle - Pasek 06

Anderle – Pasek 06

Summary Definitions [quoted from http://www.righthealth.com/topic/Fetal_Age ]:

Gestation is the period of time between conception and birth, during which the fetus grows and develops inside the mother’s womb.

Gestational age is the time measured from the first day of the woman’s last menstrual cycle [LMP] to the current date. It is measured in weeks. A normal pregnancy can range from 38 to 42 weeks.

Infants born before 37 weeks are considered premature. Infants born after 42 weeks are considered postmature. (Note: 42 x 7 = 294).

Especially with the challenged menstrual cycles that are particularly irregular in length, referencing the LMP in the reckoning can easily introduce a significant error. Perhaps that is why the above summary definition of normalcy is 38 to 42 weeks but prematurity is “before 37 weeks”? (A week here, a week there…) Read also the earlier post https://biozhena.wordpress.com/2008/01/11/about-the-edd-andor-edc-issue-and-a-request-for-input-from-readers/ .

Tomáš Císarovský  - Kukátko

Tomáš Císarovský – Kukátko

280 may have been in the Bible, but it ain’t necessarily right. We’ll see whether 266 is, and whether it is a worldwide constant, which is doubtful. If for no other reason, global constancy is doubtful because it was reported from India that “Mean gestational age at the onset of labour for women native to the area of study was 272 days (standard deviation 9 days). Pregnancies beyond a duration of 280 days showed significantly increased perinatal morbidity.” (Referencing the above righthealth.com definitions, we see 294 – 280 = 14. A week here, a couple of weeks there…)

Well, 272 – 14 = 258. Not 266, and that number is of interest because per Encyclopedia of Childhood and Adolescence, ”a gestation period of thirty-eight weeks (266 days) is calculated for women who are pregnant by a procedure such as in vitro fertilization or artificial insemination that allows them to know their exact date of conception” (article Gestation Period and Gestational Age).

And then you have the oprah.com article, which asks, “Will the labor start naturally on time, or will the baby be so late that induction or Caesarean section is necessary?”: http://www.oprah.com/relationships/Is-Pregnancy-Really-40-Weeks-Long . While debating the validity of the word “necessary” is not the point here, the author there refers to data from studies that concluded greater than 280 days due dates (288 days in one study), of which one study was in Sweden.

A hypothesis can be that hot climates may lead to lower gestation periods than cold climates. This would be a hypothesis based on two data points and a common sense for “the babies taking longer when it’s cold outside”… We’ll want to compare, say, data from Inuits and Lapps on the one hand with data from equatorial Africa and Philippines and/or Indonesia on the other. Logically, we’ll control for factors known or suspected as being involved, such as those four main causes listed above – and age, parity and other factors already explored by people such as Mittendorf in the 1980s.

Kupka - Creation de l homme

Kupka – Creation de l homme

The idea is that routine use of the Ovulona will provide for an equivalent of the above-referenced 38-week (266 days) calculation, which is available to the women receiving IVF or artificial insemination. The data will be personal and the geography of the birth will be noted (as well as ethnicity), with data sooner or later coming from all corners of the world.

Capturing and working with the fertilization date should, by and of itself, be an improvement over the current way of EDD/EDC assessment. An improvement over the paradox of modern obstetrics and gynecology handling the most important aspect of reproduction by means of some biblical myth, and having become more and more interventionist probably at least in part because of that myth. Reference a recent tweet: Maternity Care In America Rife With Systematic Failures l Being #Pregnant http://su.pr/2j91wY “most people don’t know normal birth”. This refers to the medical staff.

That these thoughts are sensible, and that the chief problem is the LMP, is supported by ultrasound studies such as “Gestational age and induction of labour for prolonged pregnancy” by Jason Gardosi, Tracey Vanner, and Andy Francis (Perinatal Research, Audit and Monitoring, Department of Obstetrics and Gynaecology, Queen’s Medical Centre, Nottingham, UK) in British Journal of Obstetrics and Gynaecology, July 1997, Vol. 104, pp. 792-797 – [http://onlinelibrary.wiley.com/doi/10.1111/j.1471-0528.1997.tb12022.x/pdf].

Citing from this study of more than 24.5 thousand pregnancies: Menstrual dates [LMP data] systematically overestimated gestational age at term when compared with scan dates… suggesting that most pregnancies which are considered ‘prolonged’ according to menstrual dates are in fact mis-dated. The median gestational age for induced labours was 286 days by last menstrual period but only 280 days by scan, and most (71.5%) inductions done post-term (> 294 days) according to menstrual dates were not post-term if scan dates alone are used to calculate the gestational age.“

This study was a retrospective analysis of computer files of 24,675 pregnancies delivered in a teaching hospital between 1988 and 1995.

Here is their graphical summary of distribution of deliveries as a function of gestational ages by ultrasound scan dates.

Deliveries vs. gestational ages by ultrasound scan dates

Deliveries vs. gestational ages by ultrasound scan dates

Their most explicit statement in support of our conviction and plan is this citation: “Even if the date of the last menstrual period is recalled with accuracy, delay in ovulation can result in over-estimation of the true gestational age, which results in an apparent prolongation of pregnancy.” The authors also cite a 1972 paper in American Journal of Obstetric and Gynecology in support of the just cited statement.

The Gardosi et al. paper concluded: Regardless of obstetric and maternal views of the advantages and disadvantages of routine induction policies, our results suggest that most post-date inductions are unwarranted on the basis of gestational age. The incidence of prolonged pregnancies can be considerably reduced by establishing dates by ultrasound alone.

Needless to say, a similar graph for deliveries in India would show the spontaneous labor peak earlier (272 days by one study in tropical Manipal) while a Scandinavian graph would be shifted in the opposite direction; both were referenced above.

I’ll be darned if the introduction of the Ovulona into the gestation arena should not bring some order and peace (as opposed to the mess and anxieties of today). As I wrote in the conclusion of the related January 11, 2008 article: It is perfectly realistic a vision that, in future, an expectant mother’s EDD and/or EDC will be assessed based on her folliculogenesis (FIV™) data.

The EDD/EDC will be computed automatically and provided by her own Ovulona Smart Sensor™. And no Saint Nicholas miraculous assistance will be required by the future users – although we will not write here the same for bioZhena.

———

* I write “allegedly” because I spent many an hour looking for evidence of truth in this allegation, only to find the Dutch man an impressive medico-scientific mind and an impressive likeable character – but no evidence of the biblical dogma ascribed to him. As I write this note, I am going once more through the tedious but interesting Dr. Boerhaave’s “Academical lectures on the theory of physic” of AD 1744. The man’s fame and authority was such that “a Chinese mandarin, seeking advice, addressed his letter to ‘Boerhaave – Europe’, and it was delivered”. See http://books.google.com/books?id=QTUVAAAAQAAJ&printsec=frontcover&dq=Hermanni+Boerhaave+1744&source=bl&ots=NCeCN4gLdd&sig=SoUA_WS6iSkh2A8WpBX7S4o54Uw&hl=en&ei=ebP-TP2WBIX2tgO12-mvCw&sa=X&oi=book_result&ct=result&resnum=4&ved=0CB8Q6AEwAw#v=onepage&q&f=false


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