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’.

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.

Infertility and A.R.T. or Assisted Reproductive Technologies

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

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

 

 

Infertility:

Clinical infertility is the inability of a couple to achieve a pregnancy or to carry a pregnancy to term after one year of unprotected intercourse. If the difficulty to conceive lasts less than a year, the condition is referred to as reduced fertility or sub-fertility (see the previous post at /2007/12/14/sub-fertility-or-reduced-fertility/ ). Clinical infertility is classified further into male infertility, female infertility, couple infertility, and unexplained infertility. Studies have shown that in the past 50 years the quality and quantity of sperm has dropped by 42% and 50% respectively. In the past 20 years the decrease in sperm counts has occurred at a rate of 2% annually. For further information refer to Xeno-estrogens (see the Alphabet of bioZhena at /2007/11/28/the-alphabet-of-biozhena/ and the web reference therein).

In the U.S. alone, of the 6.7 million women with fertility problems in 1995, 42% had received some form of infertility services. The most common services were advice and diagnostic tests, medical help to prevent miscarriage, and drugs to induce ovulation [Fam. Plann. Perspect. 2000 May-Jun;32(3):132-7].

 

 

 

A Glossary of Infertility Terms and Acronyms published by the InterNational Council on Infertility Information Dissemination is available at http://www.inciid.org/glossary.html .

 

 

ART or Assisted Reproductive Technologies:

 

Also referred to sometimes colloquially as the “heroic procedures”, they are used to treat infertility patients. ART refers to all techniques involving direct retrieval of oocytes (eggs) from the ovary. They are: artificial insemination (AI), IVF (in vitro fertilization), TET (tubal embryo transfer), ZIFT (zygote intra-fallopian transfer), GIFT (gamete intra-fallopian transfer), ICSI (intra-cytoplasmic sperm injection), blastocyst transfer and other infertility treatments, such as IUI (intra-uterine insemination), assisted hatching (AZH), and immature oocyte maturation (IOM).

Web reference: http://www.ebiztechnet.com/cgi-bin/getit/links/Health/Reproductive_Health/Infertility/Education/Assisted_Reproductive_Technologies/

 

 

Sub-fertility or Reduced Fertility

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

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

Subfertility (THE INITIAL TARGET OF BIOZHENA):

A state of less than normal fertility but not as bad as clinical infertility. Also called reduced fertility, it refers to the inability to conceive for more than about 4 months but not more than a year (which then becomes classified as clinical infertility, the inability to conceive after a year of unprotected intercourse). It is estimated that as many as one in six couples (17%) have difficulty in conceiving the number of children they want when they want them.

Again: Research suggests that between 14 and 17 percent of couples are affected by subfertility at some time during their reproductive lives. In fact, only eight out of 10 couples trying for a baby do get pregnant within 12 months. For approximately 10 percent of couples, pregnancy will still not have occurred after two years (clinical infertility). Sometimes the label of subfertility is used for couples who have had regular unprotected sexual intercourse for all of two years without conception taking place. This is a reflection of the fact that subfertility is becoming more and more commonplace.

According to one source ( http://www.womens-health.co.uk/ ), even for a healthy fertile couple, the ‘per month’ success rate (conception rate) is only around 15-20%, “so it is not at all uncommon to take some months to conceive”. Overall, around 70% of couples will have conceived by 6 months (a 30% subfertility rate). 85% conceive within 12 months (a 15% subfertility rate, “for the less impatient”). And 95% will be pregnant after 2 years of trying (technically, this is a conservatively estimated infertility rate of 5% – c.f. the 10% referenced above; or, this statistic might be perhaps considered the subfertility rate for the angelically patient). The monthly success rate in this population is 8%, and this statistic drops progressively as time goes on.

As for possible causes of difficulty to conceive, alcohol consumption, even in small amounts, can reduce a woman’s chance of conceiving by more than 50 percent, and smoking “…drastically reduced fertility in our sample”, as wrote a team from the Baltimore-based Health Care Financing Administration, in a report published in “Fertility and Sterility” (1998; 70: 632-637).

In terms of help, many people believe that fertility drugs, even when effective, remove conception from the intimate relationship between the partners, which means that it is to some extent beyond their control. Besides this loss of control, there are drawbacks and disadvantages to all forms of medically assisted conception. Some of them have potentially serious long-term effects. Consequently, many couples prefer to avoid these risks.

Women who describe overcoming infertility with the help of alternative therapists went to them because they had been offered drugs to induce ovulation but were reluctant to take them, when they learned of the possible side effects. Disturbing reports have appeared about the long-term as well as short-term effects of assisted conception. Increased miscarriage levels and premature and multiple births are not only very distressing but have considerable cost implications, both personally and societally (i.e., this is a public health issue). Babies born prematurely, or in multiple births, are at a disadvantage from the start. There are also some reports of increased rates of ovarian cancer in women who have taken fertility drugs, and of cancer in the babies of mothers who have had ovulation induced by drugs.

Subfertile couples are naturally interested in methods and tools that can help them to overcome the difficulty to conceive. The endocrinologist professor Brown may be quoted: “Failing to conceive when wanted is stressful and therefore favours infertility. It should be remembered that, apart from a few conditions such as blocked fallopian tubes, absent sperm and continued anovulation, most couples will conceive eventually without help. However, the modern expectation is one of immediate results, and the main function of assisted reproduction techniques is therefore to shorten the waiting time for conception.” To which we would add that bioZhena aims to offer a more affordable and safer alternative.

With the mentioned statistics of the fertile-age women suffering from the subfertility problem, this is a truly large opportunity in a constantly renewing and growing market. We are talking about 9 or 10 or even 18 million women in the USA alone – or quite possibly many more, taking into account all the impatience and demand for instant gratification in people today; plus about 50% of the 10 million of clinically infertile US couples, that is those who cannot afford the very costly ART treatments. [A.R.T. = Assisted Reproductive Technologies.]

This is the initial, early-stage, mission of bioZhena Corporation: To provide a definitive timing aid to couples experiencing difficulties in conceiving a baby. See also the entry for the Ovulona, where it is explained that, in this situation of reduced fertility, the basic problem is the proper timing of the intercourse.

 

Four fertility-related terms and concepts

For these and others, see the Alphabet of bioZhena at https://biozhena.files.wordpress.com/2020/01/aaee-the-alphabet-of-biozhena-011207-with-tracking.pdf

Fertile phase or fertile window:

The days of the menstrual cycle, during which sexual intercourse or insemination can result in pregnancy. It includes several days leading up to and including ovulation. The exact number of the fertile days is not known. It is currently “officially” believed to be 6 days, although evidence shows that there are only 3 days of high probability of conception (while the other three days are likely due to inadequate methods of ovulation monitoring used in earlier studies). The unequivocal determination of the fertile window is a pivotal task for bioZhena. See also the previous post: /2007/12/03/fetal-sex-preselection-%e2%80%93-illustrated/

The fertile window is an empirical factor, which should be consistent with the fertilizable lifetimes of the gametes (the egg and the sperm). Those are also uncertain but currently accepted figures are up to 12 (or maybe 24) hours for the egg, and at most 3 days for the sperm. (These times must overlap, of course; they are not additive.)

The historically excessive length of the officially recognized and advocated fertile phase has always been due to the absence of definitive diagnostic means. Some years ago, a reviewer of a federal grant application wrote to reject the proposal on the basis that the then officially recognized required period of abstinence was about two weeks, which was and is impractical, of course…

Fertility (or Fertility Status):

The female of any mammalian species, including the human female, can conceive only during a very limited period of time (a window of only a few days, arguably 3), and only if all conditions are perfect. The fertile window occurs repeatedly at intervals that are said to be more or less regular (28 + or – 9 days or so) but their variability is substantial to the extent that planned pregnancy is a challenge. A normal healthy couple will statistically take at least 3 or 4 months to conceive, even if the concept of the fertile window is known to them. An increasing percentage of couples experience difficulties in achieving pregnancy, and reproductive specialists have found that a large percentage of women had no idea of when they could conceive.

FAM (Fertility Awareness Method):

A method of determining a woman’s fertility status through self-assessment of certain fertility signs: waking temperature (also called the basal body temperature or BBT), cervical fluid, and cervical position. While NFP users abstain, FAM users apply one of the barrier methods of contraception for vaginal intercourse during the “unsafe days” of a woman’s fertile phase. NFP stands for Natural Family Planning.

Fertilization:

The joining of an egg and sperm. More accurately, fertilization is the union of a spermatozoal nucleus, of paternal origin, with an egg nucleus, of maternal origin, to form the primary nucleus of an embryo. It is the fusion of the hereditary material of two different sex cells, or gametes, each of which carries half the number of chromosomes typical of the species.

Although sperm can swim several millimeters per second, their trip to and through the fallopian tubes is assisted or facilitated by muscular contraction of the walls of the uterus and the tubes. There is also some evidence that the egg releases a chemical attractant for the sperm. In any case, sperm may reach the egg within 15 minutes of ejaculation. The trip is fraught with heavy mortality. An average human ejaculate contains several hundred million sperm but only a few hundred complete the journey. And of these, only one will succeed in entering the egg and fertilize it. Fertilization begins with the binding of a sperm cell to the outer coating of the egg (called the zona pellucida). Enzymes, released by the acrosome at the tip of the sperm head, digest a path through the zona and enable the sperm to enter the cytoplasm of the egg.

For fascinating details, there was once a developmental biology site http://zygote.swarthmore.edu/chap4.html (alas, no longer online) where one could see, e.g., a photo showing the “sun in the egg”: the microtubules (stained with fluorescent antibodies to tubulin) radiating from the centrosome associated with the male pronucleus and reaching towards the female pronucleus. “This vivid image conveyed the discovery of the moment at which a new life was formed. The metaphor expressed awareness that the force of natural powers was greater than the sum of two cells.”

Then, you can read up on Homunculus: Historiographic Misunderstandings of Preformationist Terminology, an essay by Clara Pinto-Correia, abstracted from her forthcoming book, The Ovary of Eve. This essay examines the association of the term “homunculus” with the “little man” that some of the leading spermists located inside the head of the spermatozoon during the rise of theories of reproduction in the seventeenth century. You can further find out that there is “a history of speculation about sex determination that views women as incomplete males… about the notion that women are almost-men whose development or evolution is truncated… how textbooks claimed that maleness means mastery, the Y-chromosome over the X, the medulla over the cortex, androgen over estrogen…”

The Elevator: Swiss VC/PE deal-maker offers bioZhena to their investors

The Elevator, “The Magazine for a Wealth of Opportunity”, December 2007

 

This post is about the integral and unavoidable aspect of project development – seeking development capital. The title could conceivably read “From Switzerland With Love”, if a play on words were intended. Such as the name of The Elevator magazine is a reference to the phrase “elevator pitch”, a standard concept in the venture capital/private equity arena (meaning a very brief introductory pitch of the investment proposition; The Elevator articles are naturally somewhat more extensive than that).

The editor of The Elevator reviewed and published bioZhena after we responded to their invitation, “Seeking Deals to Fund”, http://www.linkedin.com/pub/0/456/786 .

The Elevator (“The Magazine for a Wealth of Opportunity”) is an impressively produced electronic magazine, attached. On page 3, the editor writes: “…since our first issue in March 2006 we have reviewed over 300 projects and retained 60 of them as features. More than 10,000 individuals have seen The €levator ; we’ve had a great diversity of projects, much interest and several deals closed over the past 12 months. … I invite all our readers to become active members of our investor’s forum …“.

On page 35 appears the following claim: OUR TEAM OF EXPERTS PROVIDES ACCESS TO THE BEST SOLUTIONS IN PRIVATE EQUITY, ASSET MANAGEMENT AND VIP ADVISORY.

Here are the headlines from the magazine’s title page, featuring a partial list of contents, and bioZhena is one of these featured listings:

• How to open your own fund. An introduction by the experts of JP Fund Services
• bioZhena. The turnkey technology for birth control
• VentureLab. The professional matching platform
• The Village Barbados. Prime Luxury Retreat seeking USD 31 million

The interesting thing about this presentation of bioZhena, by the Geneva-area international business VC/PE deal-maker, is their risk scale. We see a scale with 6 colors, from green and light green, through yellow, then light pink and dark pink, and finally the highest risk level is red.

The editor indicates the risk level of the bioZhena proposition as between light green and yellow (or level 4 on a scale of 1 to 11). This is the same as that of the real estate deal “The Village Barbados”, and it is better than the level 5 [yellow] risk level of the VentureLab deal, and it compares favorably with the various other listings in this December issue of the Elevator. Only the Yacht Club Mediterranean and the Castellan, New York real estate deals are assessed with lower risk levels, 2 and 1 respectively.

It is also interesting that bioZhena’s risk level is assessed the same as that of DealFlow, Toronto – “a television series that captures the drama and sport of global business as seen through the eayes of dealmakers”. DealFlow “is currently seeking US$620,000 in a US$875,000 Private Placement Offering of Convertible Preferred shares at US$20.00 per share”.

bioZhena’s investment opportunity is described as follows:

Investment Volume: Up to $ 15 Million (current Offering for $3M plus 1-year $3M Warrant)

Est. Return on Investment: 100%+

Est. Duration: Approx. 3 Years

Minimum Investment: $250,000 or a portion thereof at Company’s discretion

 

Ref.:

The Elevator, “The Magazine for a Wealth of Opportunity”, December 2007

Fetal sex preselection – illustrated

In the document attached to this post (below), we say:

The following illustration is adapted from one of our slides. The slide indicates how baby gender pre-selection works or rather how it will work when the Ovulona™ is launched in the marketplace. The data were generated in a clinical study performed with our early prototype by an independent OBGYN academic. The data show the morning and evening cyclic profiles from one of the baseline subjects studied by the gynecologist Dr. Benedetto of the University of Turin, Italy.

This is a record of one menstrual cycle of a 30-years old woman participating in the Italian clinical test. The record shows the typical features of the Ovulona cyclic profile. In these early tests, the measurements were taken twice daily (morning and evening) in order to see if a time-of-day effect could be observed, and the BBT (Basal Body Temperature) was taken in the usual manner as a reference parameter.

Here is the slide:

The three-day fertile window how-to

The record shows that the features of the cyclic pattern – reproducible because the same features were also obtained by other women – make it possible to determine the boundaries of the fertile window. The precision is such that it allows for correlation of fertile day 1 with trying to conceive a boy, and correlating fertile day 3 (the ovulation day) with trying to conceive a girl. Correlating each of the 3 fertile days with the indicated likely gender of the baby conceived on the given day is based on the results of certain studies by other investigators (John France et al.), as referenced below.

The outcome of their clinical work is consistent with the finding a decade later – by other investigators in 2001 – that male spermatozoa (Y-chromosome-bearing sperm) live longer than female spermatozoa (X-chromosome-bearing). The France et al. results from timed-conception birth-giving patients stand by themselves but it is nice to have available the separately produced physiological rationale that explains those results; read on.

And here is in a nutshell the clinical trial evidence for the 3-day fertile window:

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This is a re-plot of their data (from 55 births) of birth counts as a function of the cycle day, whereby the outlier data points were considered to belong, in fact, to the counts of the three days of high birth counts, the outliers having been due to their inaccurate and unreliable methods of estimating the time of ovulation. The problem will be resolved when, instead of the old imperfect methods of guesstimating ovulation, people will use our Ovulona monitor.

More details are in the attached file: Fetal sex preselection – illustrated

The file is a description of the origin (including the best clinical trial evidence available to date) of the 3-day fertile window.

The 3-day window of high conception probability is unequivocal (there is no doubt that the data show that window). The low birth counts on the flanks of this 3-day group are data point outliers due to errors in the investigators’ estimating the ovulation day.

The 3-day group of high birth counts is in the data whether we simply ignore the outliers or add them to this group. This is no unreasonable massaging of the data because the investigators’ methods of estimating ovulation timing are well known to have high error bars associated with their ovulation-day estimation.

The 3-day fertile window is also supported by evidence published in the NIH paper referenced below. The 3 days of unequivocally high probability of conception are clear in their data, which is all based on analysis of first morning urine samples for metabolites of estrogen and progesterone that they considered “highly concordant with the peak urinary concentration of luteinizing hormone (which corresponds approximately with the day of ovulation)”.

The NIH researchers (Wilcox et al.) did not consider the inaccuracy of their estimated ovulation despite their having acknowledged that their method only “approximately” assessed the timing of ovulation. Unlike France et al., they did not use more than the one method of estimating ovulation. They simply accepted that, in addition to the three days of high conception probability, their data also contained three early days of low probability of conception – as though 3 to 5 days old spermatozoa made a woman a little bit fertile, despite the 3-day maximum lifespan of the sperm.

We account for their days of low conception probabilities in the same way as above, in terms of data point outliers. A probable cause of their low conception probabilities in the early pre-ovulation days (days -5 to -3), additional to their merely approximately estimating ovulation timing, was the possible delay between the indirectly monitored systemic hormone signals and the actual ovulation. Ovulation (day 0) in their study was not detected but only assumed based on urine hormone metabolite measurements. Despite this and other flaws in their study design, the evidence of the 3 days of high conception probability is there, similar to the data of France et al.

The Wilcox et al. technique of tracking certain ovarian hormones in the urine does not monitor the complex mechanism of folliculogenesis. Any mismatch between the ovarian and the brain hormone signals goes therefore undetected, and their estimate of ovulation timing is indeed very approximate. Of the other study design flaws, let’s mention the artifice that any “intercourse recorded on a given morning was assumed to have occurred the previous day”. This incongruous assumption artificially produced the day 1 conception probability of zero.

As for their low probability data for days -5 to -3, we can consider them to be data point outliers because a pilot study with our prototypes produced evidence of ovulation delays of up to 3 days after urinary LH detection (even 4 days in one of the 21 cycle records, monitoring urinary LH, Peak mucus, and Ovulona prototype). Ref.: https://biozhena.wordpress.com/2010/03/28/folliculogenesis-in-vivo%E2%84%A2-monitoring-is-far-better-than-current-home-use-fertility-self-help-tools/

Further, in support of the fetal gender preselection based on fertilization timing, a “statistically significant lower proportion of male births among conceptions that occur during the most fertile time of the cycle”, meaning at or near estimated ovulation, was found in a 1991 Johns Hopkins University meta-analysis of six NFP studies, cited below in the References.

Similar conclusion came out of an assessment of medical literature in 1989: “More females are conceived when coitus occurs relatively close to ovulation…”. The view of the cited group at University of Washington School of Medicine, Seattle was that the “influence of coital timing on the sex ratio is overall quite subtle and is not a practical method to alter the sex ratio for individual couples” (for citation see References). We would say that our purpose is to offer a means with which to make it practical…

Besides the referenced reviews of clinical outcomes, there is the above-mentioned evidence from a premier infertility treatment institute (G. Hodgen et al., see References) that male spermatozoa (Y-chromosome-bearing sperm) live longer than female spermatozoa (X-chromosome-bearing).

Therefore, intercourse two days before ovulation favors the conception of a boy because only the male Y-chromosome bearing spermatozoa live that long. The male sperm live long enough to be available for fertilization when ovulation releases the ovum (egg) from the ovulating ovarian follicle.

Whereas the female X-chromosome bearing spermatozoa have a chance to produce a baby girl only if intercourse takes place on the day of ovulation, because of their short lifespan.

Note that these are probabilistic indications, hence the labeling “try for a boy” and “try for a girl”. Certainly, we would not say that on the given day you will definitely conceive in your present cycle at all, let alone as indicated.

That should be no surprise because you know that conception is a matter of chance, a probabilistic matter, in the first place. More on this topic of conception probability is in the post Difficult conception tied to pregnancy complications – addressed.

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References

France et al. paper with data on fetal sex pre-selection, 3-day fertile window:

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.

Wilcox et al. NIH paper:

A.J. Wilcox, C.R. Weinberg and D.D. Berg, “Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy, and sex of the baby”, New England Journal of Medicine 333, 1517 – 1521, 1995.

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

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

Johns Hopkins University meta-analysis of six NFP studies:

R. H. Gray, “Natural family planning and sex selection: fact or fiction?”, American  Journal of Obstetrics and Gynecology 1991 Dec; 165(6 Pt 2):1982-4.

University of Washington School of Medicine review and assessment:

P. W. Zarutskie, C. H. Muller, M. Magone and M. R. Soules, “The clinical relevance of sex selection techniques”, Fertility and Sterility 1989 Dec; 52(6):891-905.