MedTech Investor: Check Out the Assumptions of Our Minimum Viable Product Scenario

In the present post, we present the bioZhena Business Assumptions. This is to draw attention to the big picture that emerges even in the Minimum Viable Scenario (MVS), the detailed assumptions of which have been worked from bottom up (with due attention to the TAM, SAM and the SOM). bioZhena Corporation’s goal is to implement the Full Value Scenario that was constructed based on the MVS. More on this in the closing paragraph of this post.

Now it’s the latter I am reaching out to. And I refer to Home Page of bioZhena’s Weblog to be reviewed in connection with the business assumptions. (Or Reproductive Health IQ Does Matter, a LinkedIn post.)

Here is a summary of the MVS, the Minimum Viable Product Scenario:

SUMMARY OF MINIMUM VIABLE SCENARIO’S SERVICEABLE AVAILABLE MARKET IN THE U.S. ALONE

US Trying-To-Conceive (TTC) Serviceable Available Market $$ at the TTC mean cost of $2,600 p.a. is $21,320,000,000

US Trying-To-Conceive Serviceable Available Market $$ at the TTC minimum cost of $200 p.a. is $1,640,000,000

US Initial Off-Label Birth Control Serviceable Available Market (SAM) $$ is $82,492,000

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Projection: FIRST PRODUCT SALES IN MONTH 16 POST FUNDING (first product application already FDA-cleared)

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Summary Comparison of Minimum Viable Scenario (MVS) with Full Value Scenario (FVS)

Click on the image for better legibility

(the URL is: https://biozhena.files.wordpress.com/2016/09/comparison-mvs-cf-fvs.pps )

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And now for the assumptions – with pictorial embellishments for dividers between the market segments.

Listing sources of market data (with some comments) followed by the resulting numerical USD market size assumptions.

‘Satyre et Bacchante’ by Jean-Jacques Pradier, marble, Palais des Beaux-Arts, Lille.

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Birth Control (BC) Market

CDC 2014 survey: 61.7% of the 60.9 million US women ages 15-49 practice contraception (= 37.6 million contraceptors), and of these 48.1% use the most common methods (the pill, sterilization, condoms, and long-acting reversible contraceptives). That leaves 38.3% or 23.32 million non-contracepting women.

un.org Trends in Contraceptive Use Worldwide 2015 Report, Annex Table II: Number of US married or in-union women using contraception = 28,600,000. Number of US women who have an unmet need for family planning = 2,560,000. Worldwide number of women using contraception is 758,000,000 and the number of women who have an unmet need for family planning is 142,000,000 (these are median data as of 2015). Couples often desire to control not just the number of children, but also the timing. We address this desire or need by design.

Next, per Guttmacher Institute 2016 fact sheet, nearly half (45% or 2.8 million) of the 6.1 million pregnancies in the U.S. were unintended in 2011 (and 42% of those ended in abortion). Contraceptive failure rate plays a big role in this. Meaning that, for 2.8 million of the 37.6 million contracepting women, their method fails (and they seek a solution). 43 million US women were at risk of unintended pregnancy in 2008. (Public expenditures on unintended pregnancies nationwide were estimated to be $21.0 billion in 2010.)

For this Minimum Value Scenario, the conservative assessment of the number of US women in the birth control market is to choose between the 43 million at risk in 2008 and the 2.8 million of unintended pregnancies in 2011 plus the 2,560,000 who have an unmet need for family planning. We choose the latter, which is much smaller, i.e. 2,800,000 plus 2,560,000 = 5,360,000 as the number of US women in the family planning (BC) market segment for our Serviceable Available Market. This is an indisputably conservative assessment of our Serviceable Obtainable Market in the birth control (BC) market segment in the U.S.

US costs of personal birth control average $1,006/year (Health Aff (Millwood) 2015 and americanprogress.org 2012). Since average ACA saving was 20%, then 100% = $ 251.5 times 5 = $ 1,257.50.  So, $ 1,257.5 – $ 251.50 = $1,006. (ACA = Affordable Care Act.) Double-check the reasonableness via this tweet.

Hence Our Birth Control (BC) Numerical Assumptions For the Minimum Value Scenario Are:

Number of US Women in the family planning (BC) market is 5,360,000

US Serviceable Available Market (SAM) $$ is $5,392,160,000

Worldwide Number of Women in the family planning (BC) market is 758,000,000

Worldwide Total Available Market $$ is very large even with only the unmet-need number of 142,000,000 women

E.g. if the estimate is based on the above US cost average, TAM is $142,852,000,000

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Initial Off-Label BC Market Upon the Ovulona Launch Assumed At 1%

Commercial market research compendium reports: The Trying-To-Conceive (TTC) tests are utilized for the unauthorized off-label use of aiding women’s natural birth control practice.

Quote: “About Half Who Use Tests Do Not Want Pregnancy”.

(http://www.marketresearch.com/Packaged-Facts-v768/Home-Medical-Tests-143386/).

Here we assume only 1% of the 8,200,000 US Fertility-Impaired Women Ages 15-44 (see below the CDC data on the TTC market), which is 82,000 women, translating at the assumed mean annual BC cost of $1,006 into an off-label $82,492,000 SAM upon the Ovulona launch into the TTC Market. To reiterate, we assume that 1% of those in the market for a tech tool aiding conception are in fact in the market to help themselves to avoid pregnancy by fertility awareness and will be off-label Ovulona users as soon as the Ovulona becomes available in the marketplace.

This is a reasonable conservative assumption in view of the 69.5 million US Catholics (the largest religious body in the United States) comprising 22% of the population^[1] as of 2015. The assumed 82,000 women represent a mere 0.1% of the Catholic population. See an example of unsolicited expression of interest in the Ovulona from a US Catholic. Ovulona market research with 5,000 US women revealed that 70% of those who would buy the Ovulona would switch from their present contraception method.

The assumed SAM [Serviceable Available Market] number of $82,492,000  represents 30.5% (but read on) of the annual retail sales of ovulation prediction kits (OPKs or LH kits) in the U.S. as they were reported in 2008/2009 when OPKs outpaced the annual sales of home pregnancy tests. The NYT article at http://www.nytimes.com/2009/04/02/business/media/02adco.html?_r=2 cited the annual OPK sales data of $270 million from IRI (Information Resources, Inc.). They derived it from in-store scanners at the retailer level for all of their major CPG clients (Consumer Packaged Goods companies) except for Wal-Mart. This info courtesy of Edward Saettone (via Linkedin Answers).

At annual growth rate of over 10% for personalized diagnostic tools (per PricewaterhouseCoopers), this suggests a SAM over $560,000,000 in 2016, and the assumed off-label SAM of $82,492,000 then represents ~15% of this documented and extrapolated figure for annual sales of OPKs in 2016. The SAM percentage (~15%) will be further reduced by the sales of the electronic ovulation predictor tests that have entered the market in the last decade or so.

For the worldwide assumption we take as base 6% of the worldwide number (758,000,000) minus the number in least developed countries (60,800,000) because: 1.  Only 6 per cent of married or in-union women worldwide used rhythm or withdrawal in 2015 (per un.org …/trendsContraceptiveUse2015Report.pdf), and 2. it is well known that especially this sub-population of women (and men) keep looking for a better tool to help them practice fertility awareness/natural family planning.  6% of 697,200,000 = 41,832,000.

Hence Our Numerical Assumptions For Off-Label Use In the Minimum Value Scenario Are:

Number of US Women off-label users upon device launch into the TTC Market segment (below) is 82,000

US Off-Label Serviceable Available Market $$ is $82,492,000

Worldwide Number of Women off-label users upon device launch is 41,832,000

Worldwide Total Available Market $$ is very large

E.g. if the estimate were based on the above US cost average, TAM is $42,082,992,000

 

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Trying-To-Conceive (TTC) Market

CDC PUBLIC HEALTH GRAND ROUNDS 2015, slide 36 titled “Impact of Lack of Insurance on Decision-Making”: Non-ART: $200 – $5,000 (and IVF: $10,000 – $15,000). Out-of-pocket costs can be substantial and impact patient decision-making and risk-taking – referring particularly to the IVF. (ART stands for Artificial Reproductive Technologies such as IVF, In Vitro Fertilization). We take $2,600 as the mean annual cost of TTC (Trying-To-Conceive, non-ART).

CDC Reproductive Health data last updated 2015: Number of US women ages 15-44 with impaired ability to get pregnant or carry a baby to term: 6.7 million or 10.9%. Number of US married women ages 15-44 who are infertile (unable to get pregnant after at least 12 consecutive months of unprotected sex): 1.5 million or 6.0%. The sum of the primary and secondary infertility sufferers in the U.S. is 8.2 million women. (Secondary infertility means that the mother has one child but cannot conceive for another.)

NIH Analysis of 277 Surveys 2012: Worldwide in 2010, 48.5 million couples were unable to have a child, of which 19.2 million couples were unable to have a first child (primary infertility), and 29.3 million couples were unable to have an additional child (secondary infertility, and the figure excludes China). Due to population growth, the number of couples suffering from infertility has increased since 1990, when 42.0 million couples were unable to have a child. Also, from WHO Evaluation Of Surveys 2004: More than 186 million ever-married women of reproductive age in developing countries were maintaining a “child wish”, translating into one in every four couples or 25%. We note this but opt for the NIH data, above.

Hence Our TTC Numerical Assumptions For the Minimum Value Scenario Are:

Number of US Fertility-Impaired Women Ages 15-44 is 8,200,000

US Serviceable Available Market $$ (at the TTC mean cost of $2,600 p.a.) is $21,320,000,000

US Serviceable Available Market $$ (at the TTC minimum cost of $200 p.a.) is $1,640,000,000

Worldwide Number of Women Who Are Unable to Have a Child is 48,500,000

Worldwide Total Available Market $$ is very large

E.g. if the estimate were based on the US non-ART cost average of $2,600 (see above), TAM is $126,100,000,000

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In closing, the reader is reminded that the above are the Assumptions for the bioZhena Minimum Value Scenario (Minimum Viable Product Scenario), which scenario represents the proverbial “low hanging fruit”. This is because our core product’s first application has FDA 510k clearance for aiding conception and for generating diagnostic menstrual profiles for physicians.

Our goal is to pursue the Full Value Scenario of the bioZhena Business Plan because of the potential of the bioZhena technology – summarized in the single slide here (the URL is:

https://biozhena.files.wordpress.com/2016/08/single-slide-biozhena-technology-potential-on-white-background1.pps ).

We aim to go well beyond personal reproductive management (which is, admittedly, where it all started, as evident from the whole bioZhena’s Weblog and our other web presence).

And for Investors – About PPM with business plan see https://biozhena.wordpress.com/and-for-investors-ppm/

And for more, you might check out  Home Page of bioZhena’s Weblog

Why screen for cervical cancer (and for the other STIs, sexually transmitted infections)?

Why all women need to screen for cervical tissue health, whether or not they accept that Nature is powerful. 

I will tell you why screening for this sexually transmitted infection (STI) is much needed, if you promise that you will not shoot the messenger. Exaggerating? Not really, if or when you realize that chances are that you yourself are already infected.

Is it so serious?

I say that because “current evidence suggests that at least 50 percent of sexually active women have been infected with one or more types of HPV”. Most people with HPV have no symptoms. When the infection is present, symptoms may or may not include genital warts.

HPV stands for Human Papilloma Virus. That is the virus that causes cervical cancer, and goes slowly about it, which is both good and bad. Good because the disease can be treated before it kills, and bad because it may take so long before it raises its ugly head that it can come completely unexpected in the mature middle age and even later. That is why vigilance (meaning, screening for it) throughout one’s lifetime is well worth it – unless you are a fatalist.

Collage of drevoryt woodcuts Dekameron, Ceský dekameron, Bakchanálie by Zdenek Mézl 1980     Links:      http://www.ikup.cz/item.php?id=600279&lan=EN        http://www.galerieart.cz/mezl_cesky_dekameron_I.JPG              http://www.galerieart.cz/prodej_mezl_staroveke_baje.htm

“Furthermore, the potential risk of infection from non-penetrative sexual contact remains undetermined, including the possible association between oral-penile contact and oral HPV, which is associated with oral cancer.” You can read this online in the peer-reviewed scientific publication Am. J. Epidemiol. (2003) 157(3): 218–226. The experts give a reference (ref. 3) for the 50%+ statistic, and elsewhere the Medical Institute for Sexual Health writes http://www.medinstitute.org/public/92.cfm  : “About half of all sexually active 18- to 22-year-old women are infected with it (ref. 10 = J Infect Dis. 2001;183(11):1554-1564)”.

Either way, let’s watch out for the killer disease, which fortunately is curable – if caught early. If not caught early (that is, if not detected, diagnosed and treated), The Ravisher wins.

Cervical cancer causes about the same number of deaths as HIV/AIDS every year [two references for this statement are cited in the above Medical Institute article http://www.medinstitute.org/public/92.cfm ].

Young Woman Attacked By Death (or The Ravisher) – Albrecht Durer

Get this! The most common STI. Both young and mature women in danger

Get this: The human papilloma virus (HPV) is the most common sexually transmitted infection (STI) in the world, and it is the most important cause of cervical cancer, a major killer of women worldwide (the second biggest).

Another horrible statistic is that, according to a CDC study, one in four (26 percent) young women, girls between the ages of 14 and 19 in the United States – or 3.2 million teenage girls – are now infected with at least one of the most common sexually transmitted diseases. Those are human papillomavirus (HPV), chlamydia, herpes simplex virus, and trichomoniasis. See http://www.sciencedaily.com/releases/2008/03/080312084645.htm .

A bad news for the mature women, who are past their best years for birthing, is this: “Cervical cancer is the second leading cause of cancer deaths among women worldwide. Human papillomavirus (HPV) has been shown to be the precursor of cervical cancer in over 99% of the cases. … Although women aged 40 and above are not specifically considered high risk for HPV infection, many women are testing positive in this age group and are facing the impact of an HPV diagnosis that implicates a sexually transmitted disease and is known to be a precursor to cervical cancer.” So is written in J Am Acad Nurse Pract. 2010 Feb; 22(2):92-100, in a paper titled “The human papillomavirus in women over 40: implications for practice and recommendations for screening”.

Arnold Böcklin, The Plague, 1898

Pap smear test. Important. But problematic

While the Pap smear diagnostic screening has significantly improved the situation over the many years since its introduction (first published by the inventor, Dr. Georgios Nicholas Papanikolaou late in the decade of “the swinging 1920s” but only recognized in the 1940s), at least 12,000 women are diagnosed with cervical cancer each year in the United States, accounting for at least 4,000 deaths. Statistics cited from J Sch Nurs. 2007 Dec; 23(6):310-4.

As commented in June 2011 at http://to.ly/aCD3 (http://www.telegraph.co.uk/news/health/news/8554793/Women-making-excuses-to-avoid-cervical-cancer-smear-tests.html ), #Cervical #cancer “smear tests are invasive, uncomfortable, embarrassing, and often are badly diagnosed”. Another reader concluded: “De-stigmatize cervical  cancer and do some work to make the test less unpleasant – more #women will go” (will go to get the expensive test at a clinic, hoping for a negative result – and for not getting an unexpected huge bill, whether insured or uninsured in the U.S.).

Additional to the advantage of an objective electronic test over the subjective evaluation of a Pap smear: Is there a better way to avoid stigmatization than testing for cervical health in the privacy of one’s home, and in so doing making the test incomparably less off-putting, painless and perfectly affordable for anyone?

Similar to what the Pap smear can do, our tissue biosensing technique should detect the pre-cancerous tissue aberration called squamous intraepithelial lesion (SIL) or dysplasia, which is the earliest form of pre-cancerous lesion recognizable by a pathologist. Refer to http://en.wikipedia.org/wiki/Carcinoma_in_situ .

Unlike the pathologist’s subjective assessment of the Pap smear sample, our in vivo monitoring method provides for an objective electronic evaluation.

In countries like India, the cervical cancer prevalence statistics are much worse, an order of magnitude higher. A big problem is that, among the general population, “knowledge about the relationship of HPV to cervical cancer is low even in the United States and the United Kingdom”. [Rapose A., Human papillomavirus and genital cancer. Indian J Dermatol Venereol Leprol 2009;75:236-44.] So therefore, we are trying to do something about that.

Screening is really necessary. Here is why

There are two main reasons why screening for cervical cancer is and will continue to be necessary.

1. One is that the recently introduced HPV vaccines are far from perfect, and they explicitly require continued screening. Even the most expert proponents of HPV vaccination, and not just the vaccine manufacturers, say and write that.

Antonín Procházka, Milenci s knihou, litografie/lithograph, 1941

2. Then there is the other reason for the necessity of continued cervical cancer vigilance. It is that, contrary to the oft trumpeted exclamations, the classic “invention of a certain doctor Condom” does not make for safe sex, because it (the condom) only reduces, and certainly does not eliminate, not only the chances of becoming pregnant but also the chances of contracting a sexually transmitted infection. These are medico-scientifically proven facts.

The condom and similar barriers do not completely and reliably eliminate the chances of pregnancy if you happen to have sex during the mere three fertile days of your menstrual cycle (when you are outside of the fertile window, pregnancy simply cannot occur). And, condoms and similar barriers do not completely eliminate – they only reduce – the chances of contracting sexually transmitted infections including HPV.

Sources, evidence – cervix is vulnerable

For sources of this statement of fact, see for example the already referenced http://www.medinstitute.org/public/92.cfm : “Each year, there are about 19 million new infections; half of these are in people under 25 (ref. 2). Many of these STIs have no cure. Untreated STIs can cause infertility, cancer and even death.” In that article is also where you see the references for the statements that “If you use condoms every time you have vaginal sex, you can cut your chance of getting HPV by up to half (references 6,7,8,9)… In women, cervical cancer causes about the same number of deaths as HIV/AIDS every year (refs. 12,13).”

Note this: Evidence shows that HPV is contracted if sex is had at too early an age and/or if sex is had promiscuously as a one night stand entertainment, or even too early into a relationship.

The cervix is particularly vulnerable to infection between the first menstruation and the age of sixteen because there are still many undifferentiated cells at the surface of the cervix, which is therefore  susceptible to HPV infection [http://www.mendeley.com/research/early-first-intercourse-risk-factor-cervical-cancer/]. As cancer is a disease of failure of regulation of tissue growth, HPV causes these cells to transform into cancer cells by altering the genes which regulate cell growth and differentiation.

Edgar Degas – Young Spartans Exercising, circa 1860

An interesting story associated with the Degas painting includes “that the work could encompass a variety of meanings”, and that the fully dressed onlookers in the background are the youths’ mothers with Lycurgus, the legendary lawgiver of Sparta, who established the military-oriented reformation of Spartan society in accordance with the Oracle of Apollo at Delphi.

Reflecting on research findings

This blog post is not some exercise in moralizing. I am merely reporting or reflecting on medico-scientific findings. The above-referenced epidemiologists, Winer et al. [Am J Epidemiol 2003;157:218-26], evaluated young college women in Washington State and found that the risk factors for acquiring a new HPV infection included:

• sex with a new person in the previous 5-8 months,
• smoking, and
• use of oral contraceptives.
• Always using condoms did not provide protection according to this study.

The experts concluded that “in this population of female university students, the risk of infection associated with new partner acquisition is independent of prior sexual experience”, and that a “…finding suggests that an increased risk of incident HPV infection is more strongly associated with sex with a new partner than with sex with ongoing partners.” Thus written.

Peter Paul Rubens – The Union of Earth and Water, c. 1618                                  For the sake of appropriate symbolism, her name should be Aphrodite or Venus, of course, the promiscuous  goddess of love, beauty and sexuality!

The authors wrote (and here we cite selected notions to reinforce the mentioned ones).

QUOTE:

• We detected a significant association between current smoking and incident HPV infection…
• We also observed a significant association between current oral contraceptive use and incident HPV infection.
• Having known a new partner for less than 8 months before vaginal intercourse was associated with an increased risk of HPV infection.
• Reporting a new sex partner who has had one or more or an unknown number of prior female sex partners was also a significant predictor of incident HPV infection.
• [Data] seems to suggest that the better and longer a woman knows her partner before intercourse, the less her risk of becoming infected with HPV.
• Consistent with previous studies (4, 7, 11, 17, 29, 30), we observed no protective effect associated with condom use. … Since HPV is transmitted presumably through skin-to-skin contact, condoms may not protect against HPV because the virus can be transmitted through non-penetrative sexual contact.
• Although vaginal intercourse is clearly the predominant mode of genital HPV transmission … any type of non-penetrative sexual contact was associated with an increased risk of HPV infection in virgins.
• At 24 months, the cumulative incidence of first-time infection was 32.3%… [FYI: That’s 32% of the 603 young women studied between September 1990 and September 1997 by interview and a standardized pelvic examination every 4 months, including HPV DNA analysis from separate cervical and vulvovaginal swab specimens.]
• Smoking, oral contraceptive use, and report of a new male sex partner –in particular, one known for less than 8 months before sex occurred or one reporting other partners– were predictive of incident infection. Always using male condoms with a new partner was not protective.
• The data show that the incidence of HPV associated with acquisition of a new sex partner is high and that non-penetrative sexual contact is a plausible route of transmission in virgins.
• HPV infections are highly prevalent, and current evidence suggests that at least 50 percent of sexually active women have been infected with one or more types (3).

In conclusion, the present study showed that the incidence of genital HPV associated with acquisition of a new sex partner is high, and that risk of infection is especially high if a partner has been known for less than 8 months and if a partner reports having had sex with other partners.

END OF QUOTES

[from Winer et al., that’s Rachel L. Winer, Shu-Kuang Lee, James P. Hughes, Diane E. Adam, Nancy B. Kiviat and Laura A. Koutsky, in Am J Epidemiol 2003;157:218-26, “Genital Human Papillomavirus Infection: Incidence and Risk Factors in a Cohort of Female University Students”. Let’s also reference http://www.google.com/search?q=Koutsky+LA%2C+Kiviat+NB.+Human+papillomavirus+infections.+In%3A+Holmes+KK%2C+Mardh+PA%2C+Sparling+PF%2C+et+al%2C+eds.+Sexually+transmitted+diseases.+3rd+ed.+New+York%2C+NY%3A+McGraw-Hill%2C+1999%3A347%E2%80%9360.+&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a].

Conclusion: Nature is powerful. Nature regulates

My conclusion for you is no preaching but an observation that all this is because Nature is powerful. As simple as that.

In terms of a clarification, or rather a rationalization of the reported findings, since you have an inkling about tissue rejection problems in organ transplantation (you’ve heard about that, haven’t you), I can draw a parallel for you. Think of the meeting of the male and female flesh as a short-lived tissue implant. If the two tissues don’t know each other, if the female has not known the male for sufficiently long, there is a natural reaction, which the cited experts have found manifested as HPV infection (a hint at how that happens: a stranger’s DNA attacks the recipient).

And what’s all this about that Nature is powerful? Well, it is simply to keep in mind that there are some natural laws and principles, such as the one about action and reaction. And, it’s about that Nature regulates…

So, there will be a reaction to too much of a good thing (or a bad thing, any thing). I don’t want to get into this too much except to recall that, since the sexual revolution of the 1960s, there has been an enormous increase in the incidence of sexually transmitted infections. Had Georgios (“Pap”) not invented his test in “the swinging ‘20s”, someone would have had to do it in the “revolutionary ‘60s”…

As it was, Mrs. Sanger had persuaded her wealthy-widow investor friend that this particular “magic bullet”, her idea of a “magic pill”, was the right approach to reproductive management. Thanks to the Pap, the Western world was sort of ready for the consequences of the Pill at least in terms of the ensuing epidemic of STDs, if not of the epidemic of infertility and of other as yet poorly recognized consequences of this fooling with Mother Nature (à la Ms. Sanger and Mrs. McCormick – “as easy to take as an aspirin”).

The fact is that “while an estimated 1 in 4 Americans will get an STD (sexually transmitted disease) in their lifetime,⁴ … the United States continues to have the highest STD rates of any country in the industrialized world.² No effective national program for STD prevention exists… and the American public remains generally unaware of the risk for STDs and the importance of prevention and screening” (per the Kaiser Family Foundation and American Social Health Association).

The National Cervical Cancer Coalition writes:

“By age 24, at least one in three sexually active people are estimated to have had an STD. Teenage girls are especially vulnerable to contracting gonorrhea and chlamydia, which can more easily infect the immature cervix.”

Perhaps you have gathered, from the various bioZhena’s Weblog articles and from our other web information, that we propose to do something about it – about making possible private screening at home for early warning devoid of the problems associated with the Pap smear test.

Oskar Kokoschka, Rejected lover, 1966

Originally, I intended to illustrate these concluding thoughts with a painting by the grandson of Sigmund Freud, Lucian or Lucien, who passed away the other day (a painting of a sad woman’s face showing from under a bed cover, with a clothed man – guess who – standing hands in pockets and just staring at her – it’s #5 in http://pul.se/muse_Cleveland-Cleveland-OH-caroline-blackwood-2LYALDu533r,d5oww4DQguiE).

But then, Oskar’s more colorful impressionist image seems, well, more colorful, and less realistic… as paintings go.

Instant detection of pregnancy and of Early Pregnancy Loss, EPL – the adversary of Trying To Conceive, TTC – especially after age 25

Early Pregnancy Loss is also known as #stillbirth or #miscarriage, or Early Embryonic Mortality (EEM), and the Ovulona™ is a tool of evidence-based personalized medicine.

After the optimum fertility age of the early twenties, achieving motherhood gets more difficult. It becomes even more essential than before to know your three fertile days, during which – and only during which – conception can occur.

The simple basic principle is: Fertility status detection must be easy and reliable. PLUS early pregnancy detection is really important, and it should be built-in, an integral part of the conception-aiding tool.

Why? Because:

1) early in pregnancy the conceived baby would be harmed by some of the medications taken by the woman, e.g. by a psychiatric medication with teratogenic effect (harmful to the fetus, causing a congenital disorder);

and 2) because of the annual 600,000 miscarriages – per CDC statistics – out of the 6 million US births, which means that at least some 10% of pregnancies are lost to early pregnancy loss (EPL), miscarriage, stillbirth.

Many EPLs go unnoticed. The EPL is a part of the TTC [Trying To Conceive] or subfertility/infertility problem. Our Ovulona monitor of FOLLICULOGENESIS IN VIVO™ is the prospective solution for managing the problem.

The Ovulona™ detects the 3 fertile days for conception, and it will also automatically detect pregnancy immediately upon conception. Similar to early pregnancy loss — its detection is the inverse of pregnancy detection, which both involve the follicular waves. Like this:

Follicular waves disappear = pregnancy detected

versus

waves reappear in early pregnancy =  early pregnancy loss detected.

Furthermore, the cyclic profile data captured by the Ovulona can be used by your healthcare provider to assess what is going on, and provide more effective help.

DIFFICULT USE OF EXISTING OPKs [Ovulation Prediction Kits] is shown in the following tweet by a @WannaBeMom: “1st month using opk. Do the lines usually start light and then get darker day by day or do they ever go back & forth b4 ovulation?”

Our electronic device will take the WannaBeMoms into a different world of baby-making.

Honey is Sweeter than Blood by Salavador Dali, 1941

For a woman in her 30s who has had a miscarriage or even two or three, “any delay in attempting conception could further decrease the chances of a healthy baby”, says CNN reporting on a medical study, http://www.cnn.com/2010/HEALTH/08/05/miscarriage.try.again.asap/ .

“Study: Women who conceive within six months of miscarriage reduce risk of another.”

November 2016 review and meta-analysis (data on more than a million women): “With an Inter Pregnancy Interval of less than 6 months, the overall risk of further miscarriage and preterm delivery  were significantly reduced.”

These are fundamental principles.

And another principle, not brought up by the CNN or by the study itself, is that a tool for monitoring the early stage of pregnancy for EPL is most desirable. We’d say, mandatory. The Ovulona device monitors (or tracks the process of) folliculogenesis in vivo, which includes the follicular waves that occur after ovulation. The waves disappear upon conception because the reproductive system does not go into another menstrual cycle – it’s pregnant.

In case of EPL, Early Pregnancy Loss (miscarriage), the waves will come back. Early Pregnancy Loss, or Early Embryonic Mortality, is quite a common sad experience of many of us.

The essential point made here is that the woman’s and her physician’s decisions should be guided by the folliculogenesis cyclic profile (and/or its distortion due to distress of any kind). The woman and her doctor should not make decisions or pass recommendations working in the dark, and the data, on which any decision should be based, must be personal to the given patient.

That’s what the Ovulona from bioZhena is for. Personalized medicine. Evidence based medicine.

Automatic pregnancy detection is inherent in the Folliculogenesis In Vivo™ cyclic profile (follicular waves disappear).

This is a screen shot of one of my narrated slides about “what’s going on here” – view (and hear) the slide at https://biozhena.files.wordpress.com/2015/07/single-slide-unprecedented-wealth-of-info-narrated.pps.

Note specifically that: The follicular waves, which occur after ovulation [when the body prepares for the next menstrual cycle], cannot remain in place after fertilization succeeds and conception takes place [because the post-ovulation regime change is even more profound]. That is the principle of instant detection of pregnancy. As opposed to the waiting for the HPT [Home Pregnancy Test] result.

HCG or Human Chorionic Gonadotropin laboratory signature of the biomarker – detected in a pregnant woman’s urine about 2 weeks into her pregnancy by a HPT home-use urine test – as a color change (into which color the HPT reduces the illustrated complex lab signature)

Should the conceptus [product of conception, early embryo] be lost to EEM, Early Embryonic Mortality (miscarriage), the follicular waves come back to be seen by the Ovulona. That’s the principle of early detection of the miscarriage, and of detecting the return of the non-pregnant condition.

Trying to conceive again should be based on the personal FIV™ [FOLLICULOGENESIS IN VIVO] cyclic profile data generated by the woman trying to have a baby. This is a principle of evidence-based medicine. Personalized medicine.

The Ovulona is intended to help people such as those writing in a forum as follows:

My partner and i started trying for a baby in jan And Concieved in the first month. Unfortunately in march at 8 weeks I had a miscarriage. We have been trying since with no luck. Could something be wrong. Please help this is really getting me down. http://www.netdoctor.co.uk/interactive/discussion/viewtopic.php?t=57881&f=5

We got pregnant the first cycle with both my ds and dd. I am most likely moving to cycle #11 with this baby. We did conceive on the second cycle of trying with baby #3 but we miscarried a week later. Nothing since then. I’m not sure why this time is taking so much longer. http://www.mothering.com/discussions/showthread.php?p=16029816

Can anyone advise? My daughter has been trying to get pregnant for several years. Her husband is fine. My daughter has now been asked to go for a scan which scared the life out of me (you automatically think something is horribly wrong). Can someone tell me what the scan is about – what sort of scan is it? http://www.netdoctor.co.uk/interactive/discussion/viewtopic.php?t=31528&f=5

The information contained in the folliculogenesis cyclic profile, as illustrated in the slide captured above, is meaningful and can help the healthcare provider to answer questions such as these.

More About Clomid, Serophene, Clomiphene citrate or Clomifene

Why popping pills is not the best. This chemicalization of life is a form of enslavement.

Expanding on the previous post, I reiterate what I left off with. It is advisable – and safer – to go about TTC, Trying To Conceive, without the use of chemicals, especially man-made chemicals – and note that herbal preparations are chemicals too. Monitoring (measuring) the effects of anything [any drug] you ingest is basically a must, if you do not play “Russian roulette” with yourself, your offspring, your family.

There is no such thing as a “magic bullet”, and every drug has side effects. It is advisable – and safer – to go about TTC by mastering the natural “right time” approach. The medical establishment has approved of it for birth control, even if not all medical schools teach it. (Go figure.)

Of course, this is the era of popping pills, but it might also be the tail of the era, if web 2 social networking and all that is really here to stay… (Please don’t say, “you wish” about the tail!) The pressure of big pharma advertizing is what makes for said era. In the Middle Ages, they who were accessible to the then lobbying pressures, had things like the Crusades, witch-hunts, and stuff like that. Now, there are different pressures and more customers accessible to them…

An Angel Leading the Crusaders to Jerusalem - Gustave Doré (1832 - 1883)

But, back to Clomid, clomiphene, now spelled clomifene. This http://www.early-pregnancy-tests.com/clomid.html is one of the many websites about the drug. It warns that “…in the case of clomid and FertilityBlend/FertilAid, the product makers do state that clomid should not be taken with herbal products…”.

Looking at the chemistry of the non-steroidal ovulatory stimulant Clomid (or clomifene), http://to.ly/5dn2, and keeping in mind the inevitable occurrence of metabolic biochemistry (drug transformation in the body of the patient), one finds this title:

Stilbenoids: Resveratrol, Tamoxifen, Diethylstilbestrol, Combretastatin, Pterostilbene, Clomifene, Stilbenoid, Combretastatin A-4, Kobophenol A – at http://to.ly/5dm1.

Simply put, these medicinal compounds are differently substituted stilbenes (http://to.ly/5dQa = chemically modified stilbenes [stilbene being an ethene double bond with phenyl groups on both carbon atoms of the double bond]). Here is the pharma business in a nutshell: The different substituents (or modifiers attached to the stilbene molecule) impart different electronic, electrochemical, biochemical and physiological activities. That’s what the pharmaceutical industry explores in or with their products.

Albrecht Durer - Christ among the Doctors. AD 1506.

Then, we have a search for triphenyl ethylene stilbene http://to.ly/5dkt . Some of the search results are as follows – with particular reference to the fourth one below the recumbent woman (where anthropogenic means “caused or produced by humans”, and endocrine, of course, pertains to an endocrine gland or its secretion into blood or lymph):

OESTROGENS AND PRO-OESTROGENS RELATED TO STILBENE AND TRIPHENYLETHYLENE http://joe.endocrinology-journals.org/cgi/content/abstract/3/1/168 . “It has recently been shown [Emmens, 1941, 1942] that oestrogensmay be divided into two classes—those which act directlyor with changes that can be effected locally…” (Yes, shown in the forties.)

Estrogens and antiestrogens I: physiology and mechanisms of action …, Volume 1 (1999) http://to.ly/5dkx . “The most prominent drug amongst these compounds is tamoxifen…”

1993: RU 486—A Decade on Today and Tomorrow http://www.nap.edu/openbook.php?record_id=2203&page=71 . “The development of RU 486¹ (Figure B1.1), the first efficient antiprogestin, may be seen as a result…this meeting, which merged science (hormone research) and the cause des femmes… it became clear that the available contraceptive methods did not completely meet the needs of women and their families; nor would they alone have a sufficient demographic impact… Mifepristone (RU 38486)…”

Albrecht Durer - Draughtsman Drawing a Recumbent Woman. 1525. Woodcut.

Chemistry of Natural and Anthropogenic Endocrine-Active Compounds http://to.ly/5dkG . “…endocrine active compounds comprise both naturally occurring substances and man-made chemicals, and their chemical structures are surprisingly diverse… Phytoestrogens, Industrial Chemicals… The stilbene-type agents diethylstilbestrol (DES), E,E-dienestrol and meso-hexestrol were synthesized in the late 1930s and are among the first man-made estrogens used for human treatment… banned today…  The phenolic A ring of steroidal estrogens has long been considered a prerequisite for estrogenicity… also of paramount importance for the high estrogenic activity of DES and other stilbene-type compounds… it has been observed that numerous other phenols exhibit hormonal activity… potential endocrine disruptors, viz., alkylphenols and bisphenols… prototype of bisphenols is bisphenol A (BPA, Fig. 12), used in large amounts for the production of polycarbonate plastics and epoxy resins… Polychlorinated biphenyls (PCBs) are among the most persistent and ubiquitous environmental pollutants. Whereas the PCBs themselves have no or at best marginal estrogenicity, significant hormonal activity may be entailed to these molecules by hydroxylation [22].”

Albrecht Durer - The Martyrdom of the Ten Thousand. AD 1508

To help make some sense of the above, let the editor of Annals of Internal Medicine (http://to.ly/5dnr ) say this: “…in the field of synthetic substitutes for the female sex hormones, the essential point is the establishment of the fact that estrogenic activity is not exclusively a property of compounds structurally similar to the natural hormones [that is, possessing the phenanthrene nucleus]… a number of simpler substances having estrogenic properties…”

So, again, there is no “magic bullet”, there are inevitable side effects, associated with lack of specificity (the scientific term for “no magic bullet”).

Specific Clomid warnings are, for example, at emedzone site (.com/clomid-brand-tabs-aventis-pharma-p-149.html). To cite: The regimen in which Clomid should be used depends on the individual condition… and if HCG was used mid-cycle or not.

Albrecht Durer - The Dresden Altar. AD 1496

Clomid Warnings

Clomid can cause disturbed vision and blurred vision and therefore should be used with caution…

For those women who are planning to get pregnant, be warned that taking Clomid may result [in] multiple births and this may be harmful to the mother and to the fetus as well. (Note: Multiple births are also a very big problem for public health.)

Clomid may also be not advised for patients with the following medical conditions (note: these are conditions that may have caused the difficulty to conceive in the first place):

• Endocrinal disorders

• Thyroid problems

• Live[r] diseases

• Ovarian cysts and enlargement

• Polycystic ovarian syndrome

• Uterine fibroids

• Any other chronic illnesses

• Endometrial carcinoma

• Vaginal bleeding

If you have any of the above-mentioned diseases, your doctor may advise you not to take Clomid or will significantly alter your dosage.

Clomid is also not advised for pregnant women as it is a drug in the pregnancy category X and may cause birth defects when taken by pregnant women.

Clomid is also not advisable for nursing mothers as it passes into the breast milk and may cause harm to the nursing infant. END QUOTE.

Albrecht Durer - Durer's Wife Agnes

In addition, the use of fertility drugs may be associated with an increased chance of developing ovarian cancer, although there is an ongoing controversy over this: http://to.ly/5dmf , http://www.wordiq.com/definition/Ovarian_cancer .

Such are the reasons why popping pills is not the best. Not to attack big pharma, but all this chemicalization of life is a form of enslavement. More insidious than the slavery that was abolished centuries ago, more subtle. First, make them buy a drug that causes such and such side effects including the least spoken of, the premature aging of the cervix http://to.ly/5dMb ; the ensuing problems are then tackled with other drugs (like clomifene), and on and on it goes.

Let’s contemplate with Albrecht’s wife Agnes why it should be that too many pregnancies were the problem before chemical contraception, whereas today… Today, sub-fertility and infertility are on the up and up, while contraceptive failure statistics are in the picture, too, showing that about half of all pregnancies in the U.S. are unplanned, and that mature population of America uses surgical sterilization for birth control.

This is a man-made problem. See the next post about accelerated atrophy of vital cervical tissues (crypts) due to the man-made problem called the Pill (About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with). And see the December 2011 post about Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s (this article reiterates and simplifies the take-home message put forward in the atrophy – aging – Mother Nature post; and two paintings of the Rape of Europa are showed there, too…).

Major studies decades ago revealed variability of menstrual cycles

But people are still naïve about the basic cause of the difficulty to achieve pregnancy

Sex education at school, its quality or otherwise, is likely to have much to do with fertility problems later in life. Many women (men, too, of course) can use the  keyboard with all their fingers (as well as their thumbs!) but have poor understanding of the basic functioning of their reproductive system.

colonial-classroom.jpg

That ignorance is well known, and is underlying the fertility problems. You should see the pregnancy doctors’ tweets – replying to some incredible questions, and then the talk of various mysteries!

A shining example is this tale of “mysterious conception”. For the whole story see the Alphabet of bioZhena under M, “Mysterious conceptions (OR THE NONEXISTENCE THEREOF)” on page 34 or thereabout, from which I cite:

QUOTE:  It appears that we must dwell on this topic, because of stories and notions propagated in various pertinent circles. This writing has been prompted by page 176 in the excellent 1999 book “Woman” by Nathalie Angier, where the Pulitzer laureate relates the story of the mysterious conception of her only child. Mysterious, because it occurred, she believes and makes her readers believe, outside of ovulation and of the fertile window.

The reason for this entry in the Alphabet of bioZhena is that there is NO SUCH THING AS MYSTERIOUS CONCEPTIONS, there is only lack of information, or ignorance of the facts. We might say, intellectual misconceptions lead to “mysteries” in terms of conception, of babies conceived supposedly when conception was biologically impossible, and vice versa, some women have difficulties conceiving for the same fundamental reason. We shall use Ms. Angier’s case to make this point. UNQUOTE.

To drive the point home, here is an excerpt from John J. McCarthy, Jr. and H.E. Rockette, “Prediction of ovulation with basal body temperature”, Journal of Reproductive Medicine, Volume 31 (No.8), Supplement, 742 – 747, 1986.

Referencing particularly large studies from 1967 and 1977, these BBT experts had this to say all those years ago (and never mind their “prediction” in the cited title whereas the BBT is well known to be no predictor):

QUOTE:  Cycle regularity is often assumed by both women and their physicians. The suggestion, that the BBT graph of the previous cycle can be used to identify the day of ovulation in the current cycle, requires nearly absolute cycle regularity. [However, note this:] The data collected by 1,085 women, who provided at least 6 or more charts each, were studied for cycle length variability. … The cycle length range was more than five days for 56% of the women who submitted 6 graphs, and for 75% of those with 12 graphs. … Absolute regularity was not demonstrated in as few as six cycles. Even when the cycle length that deviated the most was eliminated, less than 1% (8 of 1,085 women) had no variation in cycle length. When the number of cycles was extended to 12, no woman had variability of less than two days in cycle length. END OF QUOTE.

In real life, you realize, no cycle can be eliminated from the experience, and every day matters. Two days are very likely to make the difference between conception and the lack of it. And/or cause an unwanted pregnancy, for that matter.

Middendorf  – On the ball

The above findings are therefore the basis on which we can say quite categorically that nobody is as regular as a metronome (and nobody conceives in an anovulatory cycle), that there is no such thing as absolute regularity, whether 28 days or otherwise.

If you are in the sub-fertile category of people finding it difficult to become pregnant, you are likely to have cycle variability of more than 5 days over those months of your fruitless efforts that define your category. More likely than being one of the 0.74% of the population with no variation in cycle length, which under ideal conditions may also mean no variation in the time of ovulation. Persistent monitoring is well advised.

Parturition means birthing (birth) and dystocia a difficult one

And what is a parturition alarm?

For these and other entries, see the Alphabet of bioZhena at

https://biozhena.wordpress.com/2007/11/28/the-alphabet-of-biozhena/

Parturition alarm:

This is a concept that has to do with the need to know when labor or delivery is beginning, because the birthing female may be in need of help.

At the time of writing the first Alphabet draft more than five years ago, an Internet search produced only one such technology, a pressure-sensing girth, suitable for the horse breeder only, because it utilizes the fact that the horse mare lies on her side only in the process of parturition. To illustrate, we borrow a nice picture from a more recent publication found in today’s search on parturition alarm, which search still shows a preponderance of equine innovations:

In the originally noted publication, reference was made to some other method that would detect the emergence of the amniotic sac or of the foal from the vulva (vaginal orifice) but that was not a satisfactory solution. In the horse-breeding arena, about 5-6% of births require help. Various approaches to the birth alarm solution have been attempted.

These days, there are quite a few patents etc. found in the parturition alarm search. And even 5 years ago, a patent from New Mexico University should have been found because their intra-vaginal parturition alarm patent (basically for cows) was published in 1987.

In human obstetrics, where most births take place in hospitals, determining the right time of confinement would be very beneficial. bioZhena (and/or its sister company, bioPecus) will investigate our vaginal sensor technology – suitably modified – with a view to developing a parturition alarm applicable to any mammal.

Also relevant in this context is the implication of the Ovulona making available the menstrual cycle (folliculogenesis) data over many months or cycles before conception. This will enable a more accurate anticipation of the EDD, Expected Date of Delivery. You will understand this better below, under Parturition. I highly recommend that you check out Figuring Your Due Date, too – from the Midwife Archives.

Let us put it this way: Since this is the bioZhena blog (and not bioPecus, for veterinary tools), the EDD issue must be addressed first, before any parturition alarm developments. Because we are primarily concerned with the Rerum Naturare Feminina.

And it would still be of great interest to hear from an expert Latinist about the correct way of saying this in plural, the Natural Thing of Women, the Women’s Natural Thing…

This being a reference to /2007/12/16/cervix-uteri-and-seven-or-eight-related-things/ .

Parturition:

The process of giving birth; childbirth. [From Late Latin parturitio, from Latin parturitus, past participle of parturire, to be in labor.]

Parturition is illustrated at http://www.mhhe.com/biosci/esp/2001_saladin/folder_structure/re/m2/s5/ .

The illustration’s legend indicates that physicians usually calculate the gestation period (length of the pregnancy) as 280 days: 40 weeks or 10 lunar months from the last menstrual period (LMP) to the date of confinement, which is the estimated date of delivery of the infant [EDD].

Indubitably, due dates are a little-understood concept:

“Truth is, even if you know the exact date when you ovulated, you still can only estimate the baby’s unique gestational cycle to about plus or minus two weeks” [ http://www.gentlebirth.org/archives/dueDates.html ]. Why should that be? Because of the variability of your menstrual cycle lengths? (They vary even if you do not think so).

Statistically, the gestation time for human babies has a mean of 278 days and a standard deviation of 12 days, an uncomfortably large spread. The old Naegele Rule of a 40-week pregnancy was invented by a Bible-inspired botanist Harmanni Boerhaave in 1744 and later promoted by Franz Naegele in 1812. It is still believed to work fairly well as a rule of thumb for many pregnancies. However, the rule of thumb also suggests: “If your menstrual cycles are about 28 days, quite regular, and this is not your first child, your physician’s dating is probably fine. If your cycles are longer or irregular, or if this is your first child, the due date your physician has given you may be off, setting you up for all kinds of problems” (induction, interventions, C-section among them).

This is where the bioZhena technology can be expected to provide help, making it possible to reckon the EDD with recorded menstrual cycle (folliculogenesis history) data rather than merely with the LMP + 280 days. This, once properly researched, may be expected to have a significant impact on obstetric management. — Any comments?

It is ironic that, in this age of technological medicine, American women worry about their birthing process not being allowed to take its own natural course on account of an ancient method of predicting the EDD.

Ironically, the 40 week dogma – which is the gestational counterpart of the unacceptable calendar method of birth control (the so-called “Vatican roulette”) – does not reconcile the 295+ days of the 10 lunar months; and yet, at the same time, the U.S. has an unusually high perinatal death rate, resulting from high statistics of too early (preterm) labor. Quid agitur? See also under Gestation.

Dystocia or birthing difficulty:

Dystocia is difficult delivery, difficult parturition. From Latin dys-, bad, from Greek dus-, ill, hard + Greek tokos, delivery. Calf losses at birth result in a major reduction in the net calf crop. Data show that 60% of these losses are due to dystocia (defined as delayed and difficult birth) and at least 50% of these calf deaths could be prevented by timely obstetrical assistance. The USDA web site http://larrl.ars.usda.gov/physiology_history.htm is apparently no longer there but when it was it indicated that an electronic calving monitor was being developed to determine maternal and fetal stress during calving. These studies are important since they are leading the way for developing methods to reduce the $800 million calf and cow loss that occurs each year at calving in the USA’s beef herds.

In analogy with the superiority of in vivo monitoring of folliculogenesis versus tracking behavioral estrus (heat), in vivo monitoring of the progress towards parturition must be a priori a more promising approach.

The telemetric version of the BioMeter – the animal version of the Ovulona technology – will hopefully provide a tool for these efforts. Once tested on animals, human use will be a logical extension of the endeavor. (Or endeavour, should it take place in Europe! Smiley…)

Comment about the EDD and/or EDC issue, and request for input:

Again, EDD stands for Estimated Day of Delivery, while EDC stands for Estimated Day of Confinement.

Per Encyclopedia of Childhood and Adolescence, article Gestation Period and Gestational Age [ http://findarticles.com/p/articles/mi_g2602/is_0002/ai_2602000272 ], ” 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.”

The Ovulona device from bioZhena will provide to the woman user a very simple means to record the day of any intercourse. In every cycle, whether pregnancy is planned or not. This must become a part of the routine. The information will be electronically recorded along with the daily or almost-daily measurement data inherent in the use of the Ovulona. With that menstrual cycling history data, this intercourse-timing information will be available for optional use by the woman’s physician(s).

Therefore, the routine use of the Ovulona will provide for an equivalent of the above-referenced 38-week (266 days) calculation available to the women receiving IVF or artificial insemination.

This alone should be an improvement on the current way of EDD/EDC assessment.

In addition, an investigation should be undertaken into the question of whether any inference can be drawn from the woman’s menstrual cycle history prior to the conceptive intercourse. Any comments on this would be welcome, even about anecdotal or subjective or tentative observations that may be available already. However non-scientific, however tentative, however uncertain an individual answer or input from you may be…

E.g., do women with more or less regular cycles tend to exhibit a regular gestation period, and vice versa?

And, certainly, what evidence is available in medical literature (or maybe in unpublished records?) about the outcomes of the IVF and/or artificial insemination pregnancies, i.e., about their documented gestation periods? Does the 38 weeks projection work? Always? If not always, can anything be correlated with any deviation?

Do women with distinctly irregular menstrual cycles tend to have non-regular gestation periods?

The complicating effect of first versus subsequent pregnancy has already been noted, of course…

Conceivably, there is no such preliminary info available, and we shall have to try and gather even these preliminary data in a systematic manner, but – no question asked, nothing learned… Public or private input would be appreciated.

Birthday, and how it relates to the bioZhena enterprise – eukairosic™ diagnostic tools

Today is a major anniversary related to the bioZhena enterprise. Namely, a round-number (and not small) birthday of the offspring whose begetting had much, if not everything, to do with the inception of the project.

The biologically educated member of the would-be parental team insisted that medical help would have to be the very last resort, as she did not wish to be poked in and subjected to the various medical procedures available in the country of the proud Albion (that, alas, no longer ruled the waves!), where this awakening was going on. The image of what she resented getting into is telling, and it’s not even the whole story.

Awakening on the part of said couple, who till then took steps to minimize or theoretically avoid getting in the family way, owing to circumstances. As in too many instances the world over, the “awakening” was left until somewhat too late. I do not wish to talk about age specifics, but you probably know that particularly female fertility (more accurately put, fecundity or fecundability) decreases starting around or even before the Christ’s age, and so – in retrospect – it was no great surprise to find that achieving pregnancy was not as simple as expected. At the time, actually, this was a great surprise…

At the time, yours truly was not an expert in the field that deals with certain practicalities of the most important aspect of life, by which many of us mean procreation, reproduction, and its management. I am referring to some insight into the practicalities on the female side of things procreative, which insight was not there at the time – but the better half knew the basic fundamental that I now delight in referencing as eukairosic.

In a nutshell, the word refers to the right time, opportune time – exactly what we are about – the strategic or “right time; the opportune point of time at which something should be done.” A window of opportunity is kairos time.

For more about this, the Wikipedia article can be recommended, at http://en.wikipedia.org/wiki/Kairos . Let’s cite: Kairos (καιρός) is an ancient Greek word meaning the “right or opportune moment,” or “God’s time” [sic; thus said – but this should say “gods’ time”]. The ancient Greeks had many gods, and two words for time, chronos and kairos. While the former refers to chronological or sequential time, the latter signifies “a time in between”, a moment of undetermined period of time in which “something” special happens. What the special something is depends on who is using the word. END QUOTE.

If you visit that article, you will probably understand why I would like to look at the possibility of adopting as our company logo QUOTE a monochrome fresco by Mantegna at Palazzo Ducale in Mantua (about 1510 C.E.) that shows a female Kairos (most probably Occasio)… UNQUOTE.

You will also appreciate that, since we are not theologians, and because “eu-“ is the Greek prefix meaning well or good or true or easy, my choice of the adjective that we want to trademark as descriptive of bioZhena’s wares is eukairosic™.

And so here, for the sake of accurate definition, is one other item from The Alphabet of bioZhena – /2007/11/28/the-alphabet-of-biozhena/

Fecundability and fecundity:

Fecundability is the probability of achieving pregnancy within one menstrual cycle – about 20% or maybe 25% in normal couples [sic; the probability depends on many factors, including age – vide infra, or see below].

Fecundity is the ability to achieve a live birth.

Fecundability is strongly influenced by the age of the partners, and it is maximal at about age 24. There is a slight decline at ages 24 – 30, and a rapid decline after age 30.

The words are derived from Latin fecundus, fecund, from the root of fetus, via Old French fecond. Fecund means fruitful in children, or prolific.

As for the eukairosic diagnostic tools, their utility goes beyond reproductive management. Due to folliculogenesis (menstrual cycling), even things such as administration of medications or certain diagnostic examinations must be performed at the right time within the menstrual cycle…

Scire quod sciendum

fecundoscitus!!! 🙂

Thus spoke the exegete and father of Barnaby and Petrushka, Vaclav Kirsner © 2007

 ‘To know what is to be known’.

MENOPAUSE, HRT, AND BIOZHENA

For these and other terms, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

You’ll find much more there under Menopause, HRT, and bioZhena.

The Ovulona^TM is an individual woman’s health monitoring tool, primarily responsive to her steroid hormone profile. As such, it may be expected to become useful for the management of menopause, and specifically for the individualization of HRT (hormone replacement therapy) or for the monitoring of the effects of any alternative approach to menopause management. See also under Hot flushes (or flashes) and under End-organ effect, below.

The concept of individualization of HRT has to do with the adjustment of hormone dosages, so as to minimize the drugs’ harmful side effects. The bioZhena technology is an objective and quantitative monitor of the effects of steroid hormones – whether endogeneous or exogeneous (own-body-generated versus administered). On this basis, it is expected to be a meaningful tool for menopause management, both in the hands of health providers as well as conceivably in the hands of the end-users themselves. Besides causing the Ovulona to become a widely used personal tool for women’s health management in the reproductive years, there is a good chance that the technology will naturally extend its usefulness into the post-reproductive years.

Hormone replacement therapy (HRT):

The use of synthetic hormones, particularly estrogen, to replace the menopausal woman’s diminished naturally self-generated supply of hormones. Prescribed to alleviate menopausal symptoms such as hot flushes, as well as to prevent osteoporosis. Menopause and HRT – initially as “estrogen replacement” or unopposed estrogen – did not come into vogue as a topic of concern for the medical profession until the 1960s, when chemical contraception was introduced.

It is interesting to note that in countries in Asia and South America, where women eat either wild yams or soybeans, which are sources of progesterone, the term “hot flush” does not even exist in their languages. They also rarely suffer from the host of female problems presently plaguing Western women.

It is a fact that an estimated 40 to 50 million American women are now 50, the approximate average age of menopause onset. We believe that the Ovulona will be useful in menopause management in general, and personalization of HRT in particular. The latter has to do with the minimization of side effects of HRT. With respect to that, note that the risk of developing breast cancer, particularly the lobular subtype, is elevated with ‘recent long-term’ use of hormone replacement therapy. This according to a report published in the February 2002 issue of the Journal of the American Medical Association.

For more details, see Another study implicates HRT in breast cancer at http://www.lef.org/whatshot/2002_02.htm (and also http://news.bbc.co.uk/1/hi/health/3018930.stm, or google on HRT report risk of developing breast cancer).

See this April 2007 article at http://www.kaisernetwork.org/daily_reports/rep_index.cfm?DR_ID=44377, which states that as a result of said report, millions of women ceased use of the drugs. Prescriptions for HRT declined by at least 38% in 2003 and by an additional 20% in 2004. Researchers found that in 2003 and 2004, 30,000 fewer women developed breast cancer than would have been predicted by previous trends, and the incidence of breast cancer reached its lowest rate since 1987. Researchers estimate that 16,000 fewer cases of breast cancer are being diagnosed each year because of the decline in HRT use, but experts argue that HRT should not be discontinued or abandoned.

HOT FLUSHES (OR FLASHES):

During the menopausal years, many women experience severe multiple symptoms, to a greater or lesser extent, depending on the individual. In fact, 70% of women experience hot flushes within 3 months of a natural or a surgical menopause. With some, the menopausal impact of estrogen deprivation can go unnoticed. The hot flush – or, medically, the vasomotor flush – is viewed as the hallmark of the female climacteric, experienced to some degree by most menopausal women.

The term is descriptive of a sudden reddening of the skin on the head, neck and chest, which is accompanied by a feeling of intense body heat and often by profuse perspiration. The duration varies from a few seconds (about 30) to several minutes, and rarely an hour or so. The episode ends usually in profuse sweating and a cold sensation. The hot flush frequency may be from rare to recurrent every few minutes, and the flushes are more pronounced at night or during times of stress. The disturbance of sleep results in fatigue, which may in turn lead to irritability, poor concentration, impaired memory, and other deterioration of quality of life. The vasomotor flushes are less frequent and less intense in a cool environment such as in winter months in the northern hemisphere. They can occur in pre-menopause, and are a major feature of post-menopause, lasting in most women for one or two years, but in as many as 25 – 50% of women for longer than 5 years. Unlike other aspects of menopause, hot flushes lessen in frequency and intensity with advancing age.

The physiology of the hot flush is still not well understood, but it apparently originates in the hypothalamus (in the brain) and is brought about by the decline in estrogen at menopause. Vasomotor flushes appear to result from a sudden lowering of the hypothalamic thermoregulatory set point. Activation of cutaneous vasodilation (increased blood flow into skin vasculature) causes an increased peripheral blood flow and thus heat loss, leading to a fall in core temperature. There are hormonal consequences as follows: About 3 to 6 minutes after the flush onset, epinephrine increases in blood (but not norepinephrine), and corticotropin acutely rises 5 minutes after the flush onset, leading to increases in cortisol (15 minutes), androstenedione (15 minutes) and dehydroepiandrosterone, DHEA (20 minutes). While luteinizing hormone (LH) increases and peaks about 12 minutes after the onset, growth hormone also rises, about 30 minutes after the flush. On the other hand, estrogen levels, as well as prolactin, FSH and TSH (follicle-stimulating and thyroid-stimulating hormones) remain stable during hot flushes.

The flush may be preceded by palpitations or headache, and is often accompanied by weakness, faintness, or vertigo. It is understood in gynecology that 10 to 25% of women report hot flushes before menopause, and that women are often treated unnecessarily with estrogen for this relatively common psychosomatic symptom.

In brief, the flush is not a release of accumulated body heat but is a sudden inappropriate excitation of heat release mechanisms. Its relationship to the LH surge and temperature change within the brain is not well understood. It is understood that the flushes are a consequence of the withdrawal of estrogens, rather than of hypoestrogenism (low estrogen levels) per se. The discontinuation of administered estrogens may also precipitate hot flushes, which may also be caused by the infertility drug clomiphene citrate (a nonsteroidal inhibitor of estrogen receptors in the brain).

Obese women tend to be less troubled by hot flushes (because they are less hypoestrogenic).

An estimated 40 to 50 million American women are now 50, the approximate average age of menopause onset, and so it is not surprising that there is much discussion about whether hormone replacement therapy (HRT, see above) causes breast cancer or whether natural hormone creams are effective. The average woman experiencing the onset of menopause can get lost in all the controversies — especially if she is already losing her normal composure because of distressing hot flushes and night sweats.

The bioZhena technology is expected to become a useful tool for the management of menopause, and specifically for the individualization of HRT or for the monitoring of the effects of any approach to menopause management. The concept of individualization of HRT has to do with the adjustment of hormone dosages, so as to minimize the drugs’ harmful side effects.

Alternative approaches include various uses of plant products with natural estrogenic and anti-estrogenic effects that balance and augment the body’s hormone levels. For example, in The Hot Flash Cookbook (Chronicle Books, 1997), author Cathy Luchetti shares her thoroughly researched and tested nutritional solutions for relief of menopausal symptoms. In “No More Hot Flashes!” ( http://216.205.123.2/whatshot/whatshot45.shtml ), Luchetti is quoted saying, “I couldn’t accept the very idea of HRT. I have never believed in pill-popping or other synthetic approaches to health. Yet, I had to do something, because I felt as if my once-dependable body and upbeat attitude were being chiseled away, bit by bit. And being a historian, I kept recalling all the Victorian stories of menopause that ended with the woman becoming ‘unhinged by the change of life.’ I refused to accept that as my fate.”

Luchetti’s words may be considered symptomatic of the attitude of many women today, and bioZhena is in tune with these changing attitudes. Unfortunately for some, though, with addiction and consumerism being what they are, some of our “thoroughly modern Millies” (pun intended) find it almost impossible to recognize that “…to try for hot-flash relief, you should avoid certain foods if you can — especially spicy foods, caffeine, and sweets. Drinking alcohol can also trigger hot flashes”. For those, there exist some over-the-counter herbal supplements “for ridding oneself of hot flashes and other menopausal symptoms”.

As an objective and quantitative monitor of the effects of endogeneous or exogeneous (own-body-generated versus administered) steroid hormones, the bioZhena technology is expected to be a meaningful tool for menopause management, both in the hands of health providers as well as conceivably in the hands of the end-users themselves. This is a logical expectation because some women, especially those still having menstrual cycles, have apparently found that nutritional supplements (such as Dong Quai or Licorice Root) actually aggravated their symptoms. The proponents of these supplements argue that some of the herbs “don’t agree with every woman” and that it is necessary to “give it time and carefully observe its effects in your body.” As in any other situation, a good diagnostic tool is a highly advisable proposition.

End-organ effect:

A concept of biomedicine, which has to do with monitoring of the effects of stimuli, usually chemical stimuli such as drugs, on a biological system, that is either a part of or the complete body of an animal, or a human subject. While the fate of a chemical compound can be monitored by detecting it in body fluids (blood, urine, saliva, etc.), it can also be monitored by measuring the effect on a certain part of the body, called the end organ because the stimulus ends up there. The same applies to stimuli and reactions that the body generates by itself. bioZhena explores electronic monitoring of end-organ effects.

Cervix uteri and seven or eight related things

For these and other terms, see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/

Rerum Naturare Feminina. A Woman’s Natural Thing. In the lingua franca of the ancients.

The reader of this bioZhena’s Weblog article will or should be well aware that a woman’s menstrual cycle lengths are quite variable, as is the timing of her ovulation within those menstrual cycles. For evidence of this variability, see another blog post at https://biozhena.wordpress.com/2010/03/07/variability-of-menstrual-cycles-and-of-ovulation-timing/ (opens in new tab/window). Our focus on the cervix uteri is clarified below in this article.

Cervix:

The narrow lower part of the uterus (womb), with an opening that connects the uterus to the vagina. It contains special glands called the crypts that produce mucus, which helps to keep bacteria (and other microbes, including sperm for most of the cycle) out of the uterus and beyond. Sometimes called the neck of the womb, it protrudes into the vagina. The region around the cervical protrusion is known as the vaginal fornix. The sanitary vaginal tampon is inserted so as to reach into the posterior fornix. Likewise the bioZhena sensor. As simple as that.

The cervix is the gateway to the uterus and has a lot of important and challenging roles. It must allow the passage of either sperm (or penis, in some species) at copulation, prevent the entrance of microorganisms before and particularly during pregnancy, and expel the neonate and placenta at parturition (birth). It is a muscular tube that has a very dynamic role in both the menstrual cycle and in forming a tight seal during pregnancy, but opening to form a broad passageway at birth. The multitude of physiological roles of this gateway has caused it to become an important element or focus of the bioZhena technology.

Cervical mucus:

The fluid secreted by the inner walls of the cervical canal and exuded by the cervix. The amount and the properties of the fluid change depending on the phase of the menstrual cycle, e.g., from practically nonexistent during the so-called dry days early in the cycle to the relatively copious amounts of clear slippery fluid during the fertile days.

Cervical mucus is essential for the ability of the sperm to function properly: sperm survival and sperm transport within the woman’s reproductive system are critically dependent upon the presence of a healthy mucus.

To quote a noted expert, Professor Erik Odeblad: “Complications arising from the use of the Pill are very frequent. Infertility after its use for 7-15 years is a very serious problem. S crypts are very sensitive to normal and cyclical stimulation by natural oestrogens, and the Pill causes atrophy of these crypts. Fertility is impaired since the movement of sperm cells up the canal is reduced. Treatment is difficult.” He also wrote: “After 3 to 15 months of contraceptive pill use, there is a greater loss of the S crypt cells than can be replaced … A pregnancy rejuvenates the cervix by 2-3 years, but for each year the Pill is taken, the cervix ages by an extra year.” Web reference:http://www.billings-ovulation-method.org.au/act/pill.html .

Cervical mucus method:

A method of determining a woman’s fertility by observing changes in her cervical mucus. The Billings ovulation method and the Creighton model ovulation method are both cervical mucus methods.

Cervical palpation:

Feeling the cervix with the middle finger of the thus trained woman-user of FAM or NFP to determine cervical position. This is not a widely used procedure, and is not involved in the Billings and Creighton ovulation methods.

Cervical position:

Three facets of the cervix (its height, softness and the size of its opening, the cervical os) assessed for fertility significance by specially trained users of this method of NFP or FAM. Not many of those around…

Colposcope:

A viewing instrument with a bright light and magnifying lens that is used to examine the vagina and cervix stained with special solutions. Colposcopy: Examination of the vaginal and cervical epithelia by means of a colposcope. [Greek kolpos, vagina, womb + -scopy, suffix that signifies viewing; seeing; observation: as in microscopy. From Greek -skopi, from skopein, to see.] Colposcopy is the diagnostic procedure to evaluate patients whose Pap smear screening produced abnormal cytological smear results.

Billings Ovulation Method (BOM):

An NFP method in which the fertile days are identified exclusively by observations of cervical fluid at the vaginal opening. Developed by the Australian Drs. John and Evelyn Billings. An international survey in 1987 indicated that at least 50 million couples were using the method, and the number is said to be increasing from year to year. It has also been estimated that 80% of natural family planning world-wide is now the Billings ovulation method. In 1978 an international conference in Melbourne was attended by delegates from 48 countries. See also the cervical mucus method.

Creighton model ovulation method:

An NFP method of vaginal-cervical mucus self-evaluation according to criteria developed by Thomas Hilgers, M.D. at St. Louis and Creighton Universities. The criteria are called the vaginal discharge recording system (VDRS) and require that women check for the mucus by wiping the outside of their vaginas with bathroom tissue, checking the mucus for color, stretch and consistency. The last day of mucus that is either clear on appearance, stretches an inch or more, and/or causes the sensation of lubrication is called the peak mucus day. The method is similar to the Billings ovulation method.

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bioZhena’s method of monitoring the cervix:

And then we have the bioZhena method, with the Ovulona inserted briefly just like a tampon applicator, and taking a reading of the fertility status (most of the time NOT FERTILE = cannot conceive; only 3 days of fertility in each menstrual cycle):

The DIU is or will be an auxiliary add-on

 

 How the Ovulona will be transformed into a (semi-) permanently worn cervical ring obviating daily insertion is shown in slide 4 of QUICK INTRO 4 SLIDES at

Friendly Technology and Next Generation Design

The natural interest of women in being in charge of their reproductive life leads to the possibility of using the information gathered in the process for additional medical purposes. The Ovulona cyclic profile is the signature of the menstrual-cycle vital sign, which is the result of the illustrated interaction between the female brain and the ovaries – the so-called Hypothalamus-Pituitary-Gonad Feedback Loop (F). (This editing added here in 2016.)

To enlarge the image, click https://biozhena.files.wordpress.com/2009/03/menstrual-cyclic-profile-signature-of-the-hpg-feedback-mechanism.jpg

The H-P-G feedback loop (F) gives rise to the menstrual cyclic profile signatures captured by the bioZhena technology.

Here is why the bioZhena technology had to be invented. One way of saying this is: The available means, methods or products, were not good enough. Another way of putting this is to quote from medical literature, as follows.

A symposium on ovulation prediction in the treatment of infertility covered all the phenomena known to be associated with ovulation [reference 9]. Moghissi, who discussed more than 20 measurable parameters that vary during the menstrual cycle, stated the following [reference 8]: “Mid-cycle mucorrhea, ferning, spinnbarkeit, lowered cell content, and viscosity of cervical mucus are used commonly in ovulation detection and as an index of the estrogenic response of cervical epithelium. However, these changes extend over several days … (These changes) do not necessarily indicate ovulation, and are merely an index of the optimal amount of circulating estrogen…”.

In brief, none of the methods determined ovulation with the required accuracy to be useful either as a conception aid or especially for birth control. Here is how our method (monitoring folliculogenesis) does it by generating the multi-featured cyclic profile that includes the definitive ovulation marker after the predictive signals, and here is how this compares with the older techniques. See how inaccurate is the ovulation assessment by the older means available to the users of NFP or FAM (spread over 3 days):

Marquette comparison with LH kit and Peak mucus – right click on the link to open a larger PDF version of the image.

In this example, our device detected delayed ovulation while the LH ovulation kit indicated positive for ovulation on two days (not just one) and the mucus assessment (Creighton method) indicated positive one day later. The LH was positive the day before as well as on the day of the ovulation marker (day 17), while the Peak mucus day indicated ovulation one day after the ovulation marker day.

The spread of 3 days is not acceptable, but it is actually quite typical of the uncertainty associated with these older techniques. You know what that means, don’t you, because you know that every day matters. Their lack of accuracy and precision renders the older techniques not good enough – which is where we started.

Cited references:

[8] Kamran S. Moghissi, “Cervical mucus changes and ovulation prediction and detection”, Journal of Reproductive Medicine 31 (Number 8), Supplement, 748 – 753, 1986.

[9] Stephen L. Corson, guest editor, “Ovulation Prediction in the Treatment of Infertility. A Symposium”, Journal of Reproductive Medicine 32 (Number 8), Supplement, 739, 1986.

Review and listen to 3 narrated slides summarizing the bioZhena technology. Contemplate the importance of the cervix uteri.

Fetal sex pre-selection – the fundamentals

For this and the various related concepts and terms, see the Alphabet of bioZhena at

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

Fetal sex pre-selection:

Here is the underlying principle: Out of the 46 chromosomes (23 pairs), the last pair is the sex chromosome. It is of the XX type in the female and XY type in the male. The ovum (egg) has X type chromosomes only, while 50% of the sperm have X chromosomes and 50% have Y chromosomes. If an X sperm fertilizes the egg, this results in an XX combination, which is a female offspring. If a Y sperm fertilizes the egg, the result is an XY combination and a male child.

According to http://www.fertility-docs.com/fertility_gender.phtml , “the selection of gender has been a quest of couples for as far back as recorded history allows. Early drawings from prehistoric times suggest that sex selection efforts were being investigated by our earliest ancestors. Later history shows intense interest in sex selection by early Asian (Chinese), Egyptian and Greek cultures. This is followed by documented scientific efforts beginning in the 1600s to sway the chances of achieving a pregnancy by a variety of methods…” QUOTE UNQUOTE

Two approaches to sex selection have been demonstrated in the current scientific literature. One approach employs the tools and methods of assisted reproductive technologies (ARTs), manipulating the genetic material of the sperm prior to artificial insemination, so as to facilitate fertilization by the selected one of the two genders of the spermatozoa. The other approach attempts to enhance the probability of conceiving the desired gender by appropriate timing of the conception event with respect to ovulation. This is a highly controversial subject despite the fact that a substantial body of work on it has been published.

Thus, a 2001 publication by respected experts from a premier infertility treatment institute (G.Hodgen et al., see below) has put forward evidence that male spermatozoa (Y-chromosome-bearing sperm) live longer than female spermatozoa (X-chromosome-bearing).

This is consistent with earlier findings by Auckland, New Zealand researchers that boys tend to be conceived earlier in the fertile period than girls (the earlier conception requires a longer lifetime of the sperm). This was discussed in our two previous posts: /2007/12/02/regarding-fetal-sex-preselection/ and /2007/12/03/fetal-sex-preselection-illustrated/ .

A 1991 Johns Hopkins University meta-analysis of six NFP studies concluded that the data showed “a statistically significant lower proportion of male births among conceptions that occur during the most fertile time of the cycle”, meaning near ovulation.

Indeed, the Auckland study by Professor John France’s group found that 65% of male infants were conceived 2 to 5 days before ovulation while “71% of the born girls were conceived from intercourse timed between 1 day before to 1 day after the estimated time of ovulation”. This was based on 55 births. See the referenced previous posts.

Notes:

1) Hodgen et al. paper on different survival times of X and Y sperm:

Andrologia, Volume 33 Issue 4 Page 199 – July 2001
Differential binding of X- and Y-chromosome-bearing human spermatozoa to zona pellucida in vitro
Q. Van Dyk, M. C. Mahony and G. D. Hodgen

2) We might refer to the second, the correct-timing, approach to fetal sex pre-selection as eukairosic. This [Eukairosic™] with reference to http://www.perseus.tufts.edu/cgi-bin/lexindex?lookup=kairo/s〈=Greek

kairos III. more freq. of Time, exact or critical time, season, opportunity… … …

3)  France et al. paper with data on fetal sex pre-selection by timing intercourse:

J.T. France, F.M. Graham, L. Gosling, P. Hair and B.S. Knox, “Characteristics of natural conception cycles occurring in a prospective study of sex preselection: fertility awareness symptoms, hormone levels, sperm survival, and pregnancy outcome”, International Journal of Fertility 37 (4), 224 – 255, 1992.

For more about fetal sex pre-selection, see “Fetal Sex Preselection – Illustrated” at https://biozhena.wordpress.com/2007/12/03/fetal-sex-preselection-%E2%80%93-illustrated/

Fetus:

The organism that develops from the embryo at the end of about seven weeks of pregnancy and receives nourishment through the placenta. Fetus, plural fetuses:

1. The unborn young of a viviparous vertebrate having a basic structural resemblance to the adult animal. Viviparous: Giving birth to living offspring that develop within the mother’s body. Most mammals and some other animals are viviparous. Vertebrates have a backbone or spinal column.

2. In humans, the unborn young from the end of the eighth week after conception to the moment of birth, as distinguished from the earlier embryo. [From Latin fetus, offspring.]

Embryo:

The embryo is the organism that develops from the pre-embryo, and begins to share the woman’s blood supply about nine days after fertilization. Approximately one-half of all human embryos are abnormal [ http://www.columbialabs.com/html/crinwom/infertility/fertilization.htm ]. QUOTE: “There is fortuitously a biologically based selection bias against abnormal human embryos. A signal is obviously recognized by the mother, which helps explain why so many embryos fail to implant. An abnormal embryo that manages to implant is often miscarried in the first 10 weeks of pregnancy. Early miscarriages are almost always the result of abnormal development of the fetus. This is why progesterone is not usually recommended for threatened abortion. It is only if the physician can confirm, using ultrasound, that the fetus is viable, will he prescribe progesterone to help maintain the pregnancy.”

Veterinary fetal sex pre-selection:

A similarly high level of interest in embryo sexing (fetal sex pre-selection, or sex ratio) exists in the livestock industries, and researchers have experimented with the timing of insemination method. A tool such as the bioZhena Corporation’s BioMeter is indispensable for this approach to embryo sexing, because of the required accuracy and precision of the timing. The controversy in the veterinary literature is a clear evidence that timing the insemination merely with respect to estrus is not good enough. The timing must be with respect to ovulation. The BioMeter, which detects ovulation as well as anticipating it, should make it possible to investigate questions such as whether different species have different lifetimes of the sperm. It should be possible to establish what kind of a distribution of sperm lifetimes there may be within a species. (See also under Timing of insemination.)

The 2001 book Biotechnology in Animal Husbandry (R. Renaville & A. Burney, editors, Kluwer Academic Publishers) has a chapter on Sex Preselection in Mammals. The abstract states: Since a long time, sex preselection has been a goal of the dairy and meat industry to increase the rate of response to selection, to reduce the cost of progeny [offspring or descendants] testing for elite males, and to produce desired specialized and genetically superior offspring. The authors write: In animal husbandry, pre-selection of sex prior to conception will dramatically impact a farmer’s productivity and income, because in each of the chosen target industries there is a strong preference for one sex over the other. For example, the dairy industry must have females to produce milk whereas the beef industry prefers males for their higher quality and lower cost of production. Sex pre-selection is one of the most sought after biotechnologies of all times.

In a section on Factors Affecting Sex Ratio, the experts write: Considerable folklore particularly in humans has arisen regarding preconception methods to manipulate animal sex ratio. The authors point out that conventional wisdom holds that steroid hormones play no role in sex predetermination in mammals, and it is only after gonadal differentiation that steroids sculpt the characteristics, which distinguish males from females. They also write that, for a number of years, the time of insemination or mating during estrus has been believed to influence the sex ratio of offspring, and they review various conflicting reports in several animal species. One kind of these results, in cows, indicates that the sex ratio may be affected by the maturational state of the oocyte [egg] at the time of insemination (yielding sex ratio 0.7 when inseminated immediately after, and 2.5 when inseminated 8 hours after polar body extrusion, which basically refers to ovulation timing). In their Conclusion, the experts again point out that “economics dictate that livestock producers are under increasing pressure to produce a given number of progeny of the desired sex.”

The results of sex pre-selection experiments depend on the state of the ovulating egg and of the sperm. This may depend on whether a given father belongs into a sub-population of males with long or short sperm lifespan. Whether there is such a thing as this kind of categorization within a species can only be established by means of a tool such as the Ovulona/BioMeter.

This holds for all species, including Homo Sapiens, of course, and public health statistics make such categorization actually quite likely. In the U.S., the sex ratio (number of males born per 1000 females) has declined from 1.052 in 1983 to 1.049 in 1999, having been as low as 1.047 twice in the late nineties. Interestingly, this decline is evidently due to the decline in the white race (from 1.057 to 1.052, through as low as 1.049) whereas for the black race the sex ratio has actually increased over those years (from 1.028 to 1.031, through as high as 1.036) [web reference: http://www.infoplease.com/ipa/A0005083.html ].

All this is suggestive of a likely strong reason why people will want to use the bioZhena [eukairosic] products, and the application will not even need to be advertised.