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 too many young and not so young ladies could NOT receive flowers on Mothers’ Day: Why so many trying-to-conceive, why so much infertility

Say thank you to the social and medical advances of the twentieth century – primarily those of chemical birth control, the Pill.

Yes, chalk it to the great advancements! Sarcasm aside, indisputable developments in society and in medicine have resulted in the present state of affairs.

Incidentally, “Mothers’ Day (with the plural) is how it was spelled in the U.S. congressional resolution first recognizing it, 9 May 1908”. That was before all this started, before Margaret Sanger wrote “What Every Girl Should Know”, before she started a radical feminist monthly “The Woman Rebel”, and released 100,000 copies of “Family Limitation”. It was before “her confrontational style attracted even greater publicity for herself and the cause of birth control.”

Margaret Sanger
http://www.nyu.edu/projects/sanger/secure/aboutms/index.html
She wanted to liberate women.

Some years later, in the late 1920s – early 1930s, the Japanese Dr. Kyusaku Ogino (Professor at Niigata, Japan) and Dr. Hermann Knaus in Austria (University Women’s Clinic in Graz, Austria) independently discovered that women can conceive only during a brief period “in the middle of the menstrual cycle” [The Eugenics Review: Volume 28, 1936]. But – while this was the fundamental discovery of the menstrual cycle – pretty much right away there was the similarly fundamental criticism that “the so-called safe period of Knaus and Ogino offers very small protection indeed”.

That was because, for reproductive management, “the theories of Knaus and Ogino have not yet been proved sufficiently reliable for us to recommend the so-called safe period as a method of contraception…” although, “if the theory is correct, there will be more likelihood of impregnation at this time.”

Ngram 11 showing the number of English-language books with the phrase Knaus and Ogino between the years 1900 and 2008 (the latest year of available data; at smoothing 3 )
http://books.google.com/ngrams/graph?content=Knaus+and+Ogino&year_start=1900&year_end=2008&corpus=0&smoothing=3
The second, higher, peak is indicative of the relationship between the practical failure of Ogino and Knaus and the inception of the oral contraceptive pill, which provided the answer to the failure.              (For the record, the following 2008 books give good reviews of the Ogino-Knaus story in the history of reproductive management: http://books.google.com/books?id=sqwMrennRsQC&pg=PA205&dq=%22Knaus+and+Ogino%22&hl=en&sa=X&ei=39uzT5uYKeWq2QXGmrDpCA&ved=0CEgQ6AEwAg#v=onepage&q=%22Knaus%20and%20Ogino%22&f=false     AND     http://books.google.com/books?id=RmpMZ7K2L3YC&pg=PA142&dq=%22Knaus+and+Ogino%22&hl=en&sa=X&ei=JsiyT6zXCKbM2AXf3-DpCA&ved=0CEIQ6AEwAQ#v=onepage&q=%22Knaus%20and%20Ogino%22&f=false   —    found via   https://www.google.com/search?q=%22Knaus%20and%20Ogino%22&tbs=bks:1,cdr:1,cd_min:1997,cd_max:2008&lr=lang_en)

Then again, “there is a good deal of evidence to prove the existence of these fertile and sterile periods”, and an author in 1945 “gives his opinion that the period during which the mammalian egg is susceptible to fertilization may be measured”.

It was eventually – only in recent years – recognized that the extent of the fertile period should be only 3 days, and that the basic practical problem was the variability of the menstrual cycle, essentially of the follicular (“proliferative”) phase, the one before ovulation.

However, at the time we were not around with the Ovulona™ to measure the fertile period, and Mrs. Sanger’s zeal took her in the direction of a “magic pill”. In view of the failure of the first effort at natural approach to reproductive management, the so-called rhythm method, her direction is not too surprising because it was the time of great pharmaceutical advances. The chemists had the bandwagon of steroid chemistry to ride and Dr. Gregory Pincus had pioneered in vitro fertilization in the rabbit, for which he was not admired but more or less ostracized.

“In 1953, Margaret Sanger and Katharine McCormick (a heir to major millions of dollars) confronted Pincus with the idea of creating an oral contraceptive”, and the rest is history – of the Pill. History of the oral contraceptive pill and the ensuing sexual revolution. Do check out under P (Pill, the) in the Alphabet of bioZhena, and don’t miss also under M the article about “Mysterious conceptions (OR THE NONEXISTENCE THEREOF)”.

And then – now – there are the consequences of the Pill, one of which translates as the absence of the mother status in the lives of many women desiring motherhood. Those who are unsuccessfully trying to conceive, and so the bouquets of Mothers’ Day are only for their Moms.

Look how there was no infertility and no IVF before contraception. See the blue curve of infertility in the bottom graph, and the green curve of IVF in the top graph of books plotted against the years of the 20th century. See how they go up only years after the rise of contraception (bottom) and after birth control and family planning (top).

Ngrams 12 and 3 together showing the number of English-language books with the phrases birth control, family planning and IVF (Ngram 12, top) and contraception and infertility (Ngram 3, bottom)
between the years 1900 and 2008 (the latest year of available data; at smoothing 3 )
Ngram 3 data from http://books.google.com/ngrams/graph?content=birth+control&year_start=1900&year_end=2008&corpus=0&smoothing=3 , and Ngram 12 data (note: twice as high amplitude, top graph) from http://books.google.com/ngrams/graph?content=birth+control%2Cfamily+planning%2CIVF&year_start=1900&year_end=2008&corpus=0&smoothing=3

I have discussed the consequences of the steroid chemical contraception technology in several posts in this bioZhena’s Weblog. The consequences are numerous because of the far-reaching significance of tinkering with reproductive physiology – consequences for women’s health, and for public health.

Far-reaching consequences because the naturally occurring and functioning hormones, which the contraceptives tinker with, are essential for the functioning of the female organism, for the well-being of every woman.

Check out the Table of Contents = links to bioZhena posts. See, for example:

About atrophy, reproductive aging, and how it’s really not nice to fool Mother Nature – or with (For people outside of NFP [Natural Family Planning] because NFP people know this already)

The perils of IVF, of ARTs, of giving birth at old maternal age. (About epigenetic evidence that should make you think twice+ before you contemplate In Vitro Fertilization and think that having a baby can wait. The bottom line? Be a young mother!)

Difficult to conceive – Google evidence that pregnancy complications and trying-to-conceive concerns shot up after the Pill launch in 1960s (Regardless of what contraceptive proponents tell you)

Along the way to the unfortunate consequences of the anti-ovulation, anti-conception Pill and its modifications (modified methods of delivery of the chemicals into the female organism) there has been the effort to replace the calendar or rhythm method with different means of prediction of the ovulation day. I am referring to Natural Family Planning (NFP) and/or to the somewhat more recently labeled Fertility Awareness Based Methods (FABMs), one of which is the Fertility Awareness Method (FAM) itself. Fertility awareness – as opposed to the calendar – is key.

Some proponents will include NFP within FABMs and, of course, define NFP as requiring sexual abstinence during the fertile phase (aka fertile window) of the menstrual cycle; as opposed to FAM, which is defined as the use of a barrier method of contraception (such as a condom) during the fertile phase (fertile window).

Either way, the extent of the fertile window has always been THE major issue or rather the issue has always been the need for accurate and reliable determination of the fertile days. Only our Ovulona can determine the mere 3 fertile days due to the lifetimes of the sperm and of the ovum, egg. No other technique can.

Natural Family Planning or more broadly the FABMs cannot win if they continue to rely on what I have called (politely) the peri-ovulation methods of guesstimating the fertile window.

Whether used to assist conception or to avoid it, ovulation calculators, calendars and circulating hormone detectors will not do.

Scientific Fertility Assessment™ based on Follliculogenesis In Vivo™ is the only way to stop the unhealthy chemicalization of reproductive health management.

Gil Bruvel, Relative Time (1993)
http://www.liveinternet.ru/tags/surrealism/page7.html
An interesting title. Each woman has her own biological clock, which responds to her circumstances in every individual menstrual cycle. That is why there is no such thing as cycle regularity (despite the long-held simplistic belief to the contrary).
In 1970, Dr. Hugh J. Davies of Johns Hopkins University told the US Senate in the Nelson Hearings about the contraceptive Pill: “Never before in history have so many people taken such powerful medication with so little information as to its actual and potential risks. …With the introduction of such active ingredients, we are actually setting up a massive endocrinological experiment with millions of healthy women.”

Natural family planning was a significant refinement of the fundamental discovery of Ogino and Knaus, developed as an alternative to the artificial chemical contraception. For decades the NFP proponents, along with OBGYNs and birth control advocates, erred on the (off-putting) long side of guesstimating the fertile window from various signs of the approach of ovulation.

Before it was officially – and incorrectly – decided in 1995 that there were 6 fertile days (all before and including the ovulation day), the period of abstinence required by NFP was advocated as at least 10 or 13 days long. A bit too much, to say the least – and, naturally, without monitoring the variable pre-ovulation phase to quantitatively anticipate ovulation, the failure rate was too high for birth control.

Logically, the same goes for “the other side of the coin”, for conception and pregnancy achievement. Again, please see certain other posts in this blog for more – you’ll recognize the pertinent articles in the table of contents.

One example of such a post is “Major studies decades ago revealed variability of menstrual cycles” (But people are still naïve about the basic cause of the difficulty to achieve pregnancy).

The NFP and FABM approaches to birth control have managed to avoid being nicknamed “the Vatican roulette” – unlike the rhythm/calendar method of Ogino and Knaus, the pioneers of the fertile and sterile periods who discovered the menstrual cycle.

However, without our Ovulona™ the NFP and other fertility awareness methods are not reliable and, despite the NFP popularity in numerous countries, they are not any more suitable for birth avoidance than “the Vatican roulette”. Without the definitive determination of the fertile days, they are not approved for avoiding conception, and tend to be utilized for aiding conception.

That’s because, in the proceptive use (promoting conception), the methods’ lack of reliability only translates into an extended time of trying to conceive rather than into an unwanted pregnancy. Only!

Fertility awareness tends to be utilized for aiding conception by “focused intercourse” because of the high prevalence of the difficulty to conceive. And the “focus” is about all that those methods do, which helps – even if at least half is misfocused, if you take my meaning, if you see what I mean. The probability of conception increases with focus on the fertile window of opportunity. That’s fundamental, too.

People have a hard time accepting that getting pregnant is not as easy as expected, when they finally decide to want a baby – usually way too late, and after her use of the Pill. The drug makes healthy young women in their best years to postpone family- baby-making, it damages their cervical S-crypts thus causing difficulty to conceive and, by encouraging promiscuous sex life, it has caused an enormous increase in the prevalence of sexually transmitted diseases that also lead to infertility. Not just a double whammy, a triple whammy on womankind.  Sad, sad, sad.

The underlying principle of the predicament of unfulfilled yearning for a baby is highlighted in the second half of the caption accompanying the Toyen painting just below – an image of futile waiting. (Highlight extracted as the briefest of summaries from https://biozhena.wordpress.com/2010/05/25/difficult-conception-tied-to-pregnancy-complications-addressed/.)

 

Toyen, Spící (1937)
http://kultura.idnes.cz/podivejte-se-jak-vypada-marne-cekani-od-toyen-ktere-se-drazi-za-20-milionu-1ak-/vytvarneum.aspx?c=A090312_102133_vytvarneum_jaz
The painting’s title means Sleeping. The title of the referenced source, a media article, says : Look what futile waiting by Toyen looks like…
See Description of the image file for more about Toyen: https://biozhena.wordpress.com/2012/05/14/why-too-many-young-and-not-so-young-ladies-could-not-receive-flowers-on-mothers-day-why-so-many-trying-to-conceive-why-so-much-infertility/toyen-spici-1937/
It is not likely that Toyen would have had this in mind, but I present her art to highlight the predicament of unfulfilled yearning for a baby.
To highlight this:The chances of becoming pregnant are critically dependent on whether the insemination (natural or artificial) occurs at the right time, within the fertile window. This is because the probability of pregnancy is a combination of four individual probabilities:    1. Probability of being in good health,    2. of successful insemination,    3. of not miscarrying the conceptus (early embryo), and    4. the probability of correct timing of the baby-making intercourse. For example, a 60% success rate of correct timing brings the overall probability of pregnancy down to a mere 36%, and this goes down to a mere 30% if correct timing probability is only 50%, in healthy fertile couples – assuming the probability #3 (not miscarrying the conceptus) at an optimistic 75%. Even if the probability of determining the insemination time correctly were 90%, the resulting probability of successful pregnancy from any one particular insemination event would be only 55%. Get this! Only 55% under perfect ideal conditions, which include a young healthy unstressed woman.

Advanced age of the would-be Mum works against her on account of the Mother Nature’s Probabilistic Rules and Regulations of Baby-Making: Good health and successful insemination probabilities are degraded whereupon the strict Natural Eugenicist [i.e. Mother Nature] suppresses the conceptus.

So that, most often, the hCG pregnancy marker does not even have a chance to be detected – after the nerve-wracking 2-week wait – by the not-so-young Mum-candidate’s HPT [Home Pregnancy Test].

Needless to say that, all the more the not-so-young motherhood aspirant needs to enhance the fourth element of the equation, the probability of correct timing of the hoping-for-baby sexual intercourse.

And all this because the young lady used the Pill during the years best suited for baby-making, and as a consequence she is not-so-young any more. It’s not nice to fool Mother Nature! Or with…

Therefore, I conclude this blog post by disputing the positive and admiring message in the concluding paragraph in the above-cited article “The Birth of The Pill”. They write: “Margaret Sanger dreamt of the idea of a birth control pill since she was a young woman. If she wasn’t confined to the boundaries of her time, she and McCormick could’ve researched and funded The Pill without the help of any male doctors or scientists. Unfortunately, the society that they lived in would not allow them to do so; they did go as far as they could. Many of their achievements go unnoticed, but both women were really the leading forces behind the development of The Pill.” QUOTE UNQUOTE.

Yes, indeed, Margaret Sanger and Katharine McCormick were the leading forces in the inception of chemical contraception. Driven by a social, political agenda (with “can do” in lieu of the needed biomedical insight), they imposed on women, and hence on humankind, a simple-minded solution “as simple as taking an aspirin”. But, then… the consequences … among them an enormous increase in the incidence of sexually transmitted infections, contributing to the epidemic of infertility.

And that’s only for openers, as the saying goes. Referring to https://biozhena.wordpress.com/2012/04/18/the-perils-of-ivf-of-arts-of-giving-birth-at-old-age-part-2/: Detrimental effects on the offspring and – via epigenetics – on the health of future generations. Iatrogenic medicine kicking Hippocrates where it hurts the most. Also, therefore, quite the opposite effects with respect to the eugenic vision of Mrs. Sanger. Ironic, isn’t it.

The fallacy of ovulation calculators, calendars and circulating-hormone detectors

Don’t let them lead you by the nose with likely this and probable that! You need to know for sure.

When it comes to the crucial timing of ovulation, it is astonishing to see the fallacies and delusions propagated on the web – and that this includes even certain generally respected mainstream sources. How they declare, for example: If you’re trying to get pregnant, use this tool to find out when you likely ovulate and are most fertile.

Never mind that “most fertile” makes absolutely no sense because there is no such thing as a little fertile, more fertile and most fertile!

Ladies (and teenage young ladies included!), you either are fertile today or you are not: You either can conceive today or not.

It is either or.

You either are fertile today or you are not. It is not a little bit fertile, or more fertile, or most fertile. Like, you cannot be a little bit pregnant… you either are, or you are not.

Besides which, if you want to conceive a pregnancy, you must know with certainty that ovulation happens when you try to conceive – not merely that it is likely to happen. Unless you are reproductively ill or menopausal, it is always likely to happen at some point but the mere likelihood is not very helpful. Conception absolutely requires ovulation so that the released (ovulated) egg has a chance to be fertilized.

You must have a way of detecting ovulation at home and, based on that instrumentally recorded information, we will also help you with the Expected Date of Delivery (EDD), because that is how it works. Not the LMP (Last Menstrual Period) but the date of the conceptive ovulation — that’s the ovulation with which you became pregnant because your ovulated egg became fertilized. The date of ovulation is the date from which the EDD must be computed.

Ovulation caught on camera by Dr. Donnez – impressive but not a practical method of detecting ovulation

Fast forward to the principle that’s behind the take-home message of this post and that’s systematically arrived at by the end of this post:

Briefly: Tracking systemic effects (hormones in circulation) is not good enough for fertility status determination, especially if the purpose is pregnancy avoidance.

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To be blunt about the language of “likely ovulate” and “most fertile”: Such language simply reflects their inability to be definitive about it – and they therefore resort to guesstimating ovulation, calling it a calculation.

Numerous websites proffer their ovulation calculators when you search online for “ovulation”. A free, printable ovulation calendar and ovulation calculator to help you…, ovulation calculator can help you find the best time to conceive (as if there was some worse time when to conceive!), a calculator to generate your ovulation calendar and determine the best time…, our free Ovulation Calendar helps you predict your most fertile time of the month (ovulation) so that you can achieve pregnancy. Etc.

Notably and significantly, they do NOT promote this for natural (behavioral) pregnancy avoidance (birth control) but only as a tool for assisting conception – as if these were not the two sides of the same coin. They do not because they would get into trouble if they did.

A common approach relies on detecting, in a woman’s urine, the luteinizing hormone (LH) that typically surges on the ovulation day. The LH surge (sharp narrow peak in LH concentration) occurs a few hours before ovulation. Because that is really too late for anticipating ovulation, a related but more sophisticated fertility monitor additionally detects also a metabolite of estrogen, i.e., another hormone, which anticipates the LH surge by about a day.

The worst flaw of systemic hormone monitoring

Fundamentally the most serious detriment is the fact that ovulation as such is not detected by said fertility device or any other such available in the marketplace. Ovulation is merely assumed to occur some hours after the LH surge – but the surge of the LH hormone is merely a trigger signal sent by the brain to the ovary. It says, “ovary, let go of the ovum in our dominant follicle”, but it does not say that the ovary in fact did (or does).

This is a fundamental flaw because ovulation is known to fail to occur in approximately 20% of the follicles. Those follicles, triggered by the LH, undergo the cyclic event of follicle rupture but, despite the rupture, the egg does not come out – there is no ovulation.

In 20% of LH-triggered cases, the egg is not released so ovulation, as photographed here by Dr. Donnez, does not occur

Ovulation also fails to occur with another type of follicles, the so-called luteinized unruptured follicles. Yet, the LH surge can be seen in either case, and is therefore a false indicator.

Furthermore, when stress causes a delay of ovulation or absence of ovulation despite the LH surge signal (signal from the brain to the ovary), this cannot be detected and handled by the urinary hormone-based approach. As you can imagine, with our stressful lifestyle and environment, this is a very serious flaw that results in many disappointments. Our technology will make a big difference in managing the situation.

George Condo – Field of Figures sold for $450,000 at Skarstedt Gallery’s booth Published: June 14, 2011

Since, unlike our Ovulona™ Smart Sensor™ technology, their method depends on biochemical reagents and since the supply of the reagents is limited, their product’s user has to estimate on which day of her menstrual cycle she should start using the hormone-monitoring device when peeing into a cup. She does the estimating based on her previous menstrual cycle(s) as though the length and the timing of the present menstrual cycle were the same as in her previous cycle(s). Alas, that’s not so. Because of the variable lengths of successive cycles in most women, this is a weak feature in their design (even though they are getting away with it).

A key practical problem of the referenced 2-hormone device (the Clearblue® Fertility Monitor) is that the monitored urinary concentration of the estrogen metabolite E3G peaks only about 12 to 24 hours prior to the LH surge. This is not early enough to serve as a marker of the beginning of the fertile phase.

Fertile day 1 not identified

Their research or marketing literature may claim that “a sustained rise in E3G can be used to identify the start of the fertile phase”, referring to the slow gradual increase that eventually becomes the peak of E3G concentration. However, the idea to use an ill-defined rise – rather than the peak in the cyclic profile of the estrogen metabolite – is not a viable solution to the fertile window problem.

Even if the ill-defined E3G rise in the urine were correlated with a clearly defined stage of the egg development towards ovulation, a serious problem is that the rate of the E3G rise differs from cycle to cycle, as do the blood concentrations of E3G. The initially slow increase of the E3G concentration in the urine proceeds at different rates in different cycles, not only at different rates in different women. The E3G rise cannot be predictably associated with the beginning of the fertile period, and it cannot serve as a marker.

Schematic diagram of interaction between the LH and FSH hormone-generating glands in the brain (hypothalamus and pituitary) and those of the ovary (female gonad) generating estrogen and progesterone

The reasons are as follows:

1. Estrogen is known to have both stimulatory and inhibitory effects on LH secretion and, to be effective as a stimulant, it must rise to its peak levels (> 150 to 200 pg/ml) and must remain elevated for at least 36 hours [J. Hotchkiss and E. Knobil in E.Y. Adashi, J.A. Rock and Z. Rosenwaks, editors: Reproductive Endocrinology, Surgery and Technology, Lippincott-Raven Publishers, 1996].

In fact, the E3G rise indicates something else:

2. The E3G profile does not reflect the local interplay of estrogen with progesterone because it only reflects clearance of one of at least 10 metabolites of estrogen from peripheral blood circulation into the urine, after oxidative conversion in the liver.

Whatever the rate of this clearance process in the given woman in the given menstrual cycle, there are “local mechanisms due to which the quantification of ovarian steroids in peripheral blood or in urine is rendered interesting but of little value in predicting the genital end-organ effect” [C.J. Verco, in A.M. Siegler, editor: The Fallopian Tube. Basic Studies and Clinical Contributions, Futura Publishing Company, 1986].

The decades old problem is fundamental

This makes for the same basic flaw as that suffered by other monitors of peripheral hormones whether the hormone be progesterone (BBT monitoring) or estrogen (conductivity of saliva or of vaginal fluids).

Thus, the 2-hormone approach is in the end as inaccurate as the other LH-detecting techniques (the OPKs, Ovulation Predictor Kits). Therefore, like the other hormone monitoring methods, it cannot be approved and proffered for pregnancy avoidance since the failure rate would be unacceptably high. In fact, a law suit ensued in England, when the original developer company did sell the LH-and-estrogen monitor as a “contraceptive system”, and a number of unintended pregnancies resulted to the users.

See also below, under “Smart phone apps with the BBT?” the link about Natural Cycles – the app that got regulatory approval for contraception after their clinical trial with women who purchased the app because they believed they had “regular cycles” of constant cycle length.  Not surprisingly, problems and unwanted pregnancies ensued.

The fundamental point is this: The effects of the local and acute regulatory mechanisms (referenced under 2 just above) remain undetected by the old techniques that work with the peripheral biomarker variables.

Ovarian vein-to-artery exchange of steroids, prostaglandins and other bioactive substances is a local transfer mechanism which enables local regulation of ovarian, tubal and uterine functions. The local, as opposed to peripheral, blood concentrations of the steroid hormones are also believed to work with the innervation of the female genital tract (the cervix in particular).

The effects of these local and acute regulatory mechanisms remain undetected by the old so-called prior art techniques that work with peripheral biomarker variables. In contrast, our Ovulona™ detects them – via the cervix, the natural monitor of the female reproductive system.

Gustav Klimt – Medicine mural – Klimt’s primary subject was the female body

The flawed assumption of similar timing of menstrual cyclic events from one cycle to another has been a problem for the BBT and the BBT thermometers. Since the late sixties, the microprocessor technology has been applied by a number of people to the well-tried basal body temperature [BBT] approach to family planning that was originally hoped to work for pregnancy avoidance.

Smart phone apps with the BBT?

The BBT approach is no longer recognized as medically valid even if it may be acceptable to some of the older physicians, and to the younger buyers of an expensive microcomputerized BBT monitor offered from Europe and/or to the users of the more recent smart phone apps based on BBT monitoring.

This is because the so-called basal body temperature is a systemic variable that reflects, among other things, progesterone rise in peripheral blood after ovulation, usually one or two days later.  It is a very indirect and non-specific biomarker. Even though in some women in some cycles a little-understood dip in the temperature graph may apparently be observed one day before the temperature rise, it is clear that the BBT method is of little value due to its lack of predictive capability and due to its fundamental unreliability. The BBT-rise data is known to have a large error bar since the rise can occur from 3 days before to 3 days after ovulation.

For a more detailed critique of the BBT monitoring approach and a rebuttal of a particular European product, peruse Critique of BBT monitoring – DuoFertility rebuttal. Also read a note on 3 things that differentiate our technique from the smartphone apps and particularly the most recent, Natural Cycles .

Briefly: Tracking systemic effects (hormones in circulation) is not good enough for fertility status determination, especially if the purpose is pregnancy avoidance.

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Purveyors of the old “prior art” technologies get away with it because of the high demand for any help with the serious and growing problem of sub-fertility, more commonly called trying-to-conceive or difficult getting pregnant. When the purveyors publish anecdotal evidence of “efficacy” in the form of thank-you letters from women who did achieve pregnancy, we should keep in mind that the women received help in focusing on trying to hit the fertile period regardless of whether the given technology actually did work or not.

If any of the “prior art” did work reliably, it would be used as a pregnancy-avoidance tool, which is not the case (with the one exception noted above, a reservation included suggesting that only women with self-assessed regular cycles opted to buy the BBT-and-calendar based app with its 11 “unsafe” days offered to the user instead of the true fertile window).

Venus, Cupid, Folly, and Time (also called An Allegory of Venus and Cupid and A Triumph of Venus) is an allegorical painting by the Florentine artist Agnolo Bronzino – circa 1545.  The bearded bald figure to the upper right is believed to be Time…

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Now go see about “Instant detection of pregnancy and of Early Pregnancy Loss, EPL – the adversary of Trying To Conceive, TTC – especially after age 25″ at https://biozhena.wordpress.com/2010/11/11/instant-detection-of-pregnancy-and-of-early-pregnancy-loss-epl-the-adversary-of-trying-to-conceive-ttc-especially-after-age-25/

And should you be an investor and/or wish to find out more, check out  Home Page of bioZhena’s Weblog

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Further peri-vernal equinox tweets on #conceiving, kairos time and #fertility, achieving #pregnancy, caution about in vitro & appearances

And NFP users still know that fertility awareness

is for birth control, too

As previously noted, language aware readers and subject matter aficionados know that the “peri” in the title does not refer to any “one of a large group of beautiful, fairylike beings of Persian mythology …” nor, for that matter, to “any lovely, graceful person” such as you are.

You already know that “peri” is a prefix meaning “about” or “around” and “near”, appearing in loanwords from Greek [http://dictionary.reference.com/browse/peri]. Just like here, whereby we take notice of the Spring Equinox – when the Sun rises exactly in the east, travels through the sky for exactly 12 hours and sets exactly in the west – this year on March 20 “, today.

And, “anyone standing on the equator at noon will not cast a shadow” [http://www.wilsonsalmanac.com/book/mar20.html]. Lovely thought [entertained in snowbound Colorado Rockies]! Then another idea, not necessarily lovely – but a key concept: The dictionary does not tell that this is one of the instances of “kairos time” of the Earth! For the meaning of “kairos time” you can check out an earlier post here, https://biozhena.wordpress.com/2007/12/28/birthday-and-how-it-relates-to-the-biozhena-enterprise-%E2%80%93-eukairosic%E2%84%A2-diagnostic-tools

Spring Equinox (aka rovnodennost)

But now for some more of the tweets (again a little edited, since here we do not have the 140 character limit. And still – in the usual manner – with clickable links to further information, including more tweets of all sorts via the #hash tags).

Do you chart your #fertility cycles? If so, would you like to include our FIV cyclic profile http://to.ly/VCF in your charts? Do let me know if interested #pregnancy #birth 7:24 PM Mar 16th

If you have not yet explored bioZhena’s Weblog http://to.ly/vUz do visit http://to.ly/1kXE Variability of menstrual cycles and ovulation timing. Read on kairos time. 8:05 PM Mar 16th

A collage that depicts our message. After disappointments, once you determine your exact “kairos time” in the cycle you want to conceive in, you’ll get the #pregnancy you wish for http://tweetphoto.com/14671191 8:38 PM Mar 16th

Collage of 3 pics with 15-WordlegreetingsfrombioZhenasf-3.jpg

Mistiming intercourse is the chief cause of apparent #infertility http://to.ly/1ppi . With a certain Fertility Monitor, they claim that 50% of users got #pregnant in the 1st cycle, and 92% in the 3rd. 196 women provided this statistic, out of 276 women asked. “The issue of early intervention with [clinical] tests and medications were highlighted, resulting in escalating costs and strain on the couple.”  2:02 AM Mar 17th

RT@bioZhena Compare the cost of the certain Fertility Monitor, which – unlike ours – requires monthly reagent sticks, from ~$250 (1cycle) to some $550 (10 cycles). Compare that to the average cost of ART medical treatment, which they report was $6,637 for the surveyed women, with a median medical evaluation cost $1,075 per cycle 2:06 AM Mar 17th

... with a median medical evaluation cost $1,075 per cycle ...

Numerous papers http://to.ly/1pq1 show improved #pregnancy rates and effective #birth control with #fertility monitors. That is with focus on determining the #fertile window 2:20 AM Mar 17th

Statisticians reported on day-specific probabilities of #pregnancy with data from 2 studies that used what they called (correctly) Imperfect Measures of ovulation http://to.ly/1pqh They did not ask: Perfect Measure of ovulation soon? 2:34 AM Mar 17th

*Perfect Measure*of ovulation resides in deterministic versus statistical approach.  *Imperfect* (fuzzy) replaced by accurate #fertility determination that indicates the first fertile day and the last fertile day, day 1, day 2, day 3, boom, boom, boom 2:49 AM Mar 17th

Fertile window as determined by the Ovulona, and how it compares with the BBT

You should understand: No in vitro diagnostics (out of body), no circulating hormones like LH and/or estrogen can ever make a RELIABLE #fertility monitoring method – because fertility is the result of a complex integration or interplay of numerous neuroendocrinological signals. This or that hormone in a body fluid does not do that. (It’s merely one of many input signals. In case of the BBT, more like an output.)

Similar caution applies to NFP observations of #fertility signs. Mucus is a measure of estrogen. It does NOT show the boundaries of the #fertile window, it only indicates ovulation is likely, but not when, and not really if

Your #cervix receives #fertility signals from the active ovary and from your brain. But understand that the cervix appearance and feel only indicates approaching #ovulation, not ovulation as such

The appearance of the cervix, like (the appearance of) ovarian ultrasound will indicate that ovulation was yesterday. Or, more accurately put, ultrasound indicates that the follicle collapsed and PERHAPS (80% probability) released the egg

Monitoring your #fertility signs is better than nothing BUT if it’s not helping you to get #pregnant, it will #stress you out and make things worse

Until you use a definitive deterministic tool, “better than nothing” is arguable if you take it from the statisticians that having intercourse about every day for 20 days is 60% likely to result in conception

Of course, you would still have ~40% probability of not achieving #pregnancy so what is new. That is the meaning of #subfertility. Need a solid tool that determines the 3-day fertile window, boom, boom, boom (but stress may prolong this – in a detectable manner).

Our deterministic tool avoids statistics and probabilities, and detects ovulation after anticipating it from what the cervix is saying electronically now, in this cycle. Most of the time not fertile, and then for a few precious days, #fertile

Songs of Innocence and of Experience

To sum up: Appearances are no real measures, they are only approximate.  Approximate is not good enough for #fertility status – to get #pregnant or, especially, to avoid getting pregnant. And, especially, if you want to try for a desired baby gender.

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FOR MORE ABOUT ALL THIS GO TO THE 2012 ARTICLE https://biozhena.wordpress.com/2012/02/13/the-fallacy-of-ovulation-calculators-calendars-and-circulating-hormone-detectors/ = The fallacy of ovulation calculators, calendars and circulating-hormone detectors. Don’t let them lead you by the nose with likely this and probable that! You need to know for sure.