Posts Tagged ‘women’s’

MENOPAUSE, HRT, AND BIOZHENA

December 18, 2007

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

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

Klimt’s Medicine mural

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

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

Hormone replacement therapy (HRT):

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

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

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

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

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

HOT FLUSHES (OR FLASHES):

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

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

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

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

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

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

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

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

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

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

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

Michelangelo’s Sybille de Cummes

End-organ effect:

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

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Premenstrual syndrome (PMS) and PMDD

December 17, 2007

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

The bioZhena technology is useful beyond the fertility-tracking primary purposes

(i.e., beyond aiding conception and aiding birth control).

“PMS is one of the most common disorders treated by reproductive endocrinologists”

The Book of Urizen

PMS is a combination of emotional, physical, psychological, and mood disturbances that occur after ovulation and normally end with the onset of the menstrual flow. The symptoms include abdominal bloating, breast tenderness, headache, fatigue, irritability, anxiety, and depression.

Why is this serious?

At least 30% of menstruating women experience distressing premenstrual symptoms that compel them to seek their doctor’s help, and as many as 60% to 75% of women experience some of the PMS symptoms. Of these, about 2% to 10% experience severe problems and functional impairment, which is called the premenstrual dysphoric disorder or PMDD.

According to the PMS expert, Dr. Joseph Mortola, PMS is one of the most common disorders treated by reproductive endocrinologists. Diagnosis depends on prospective recording of symptoms, and a documented symptom-free interval during the follicular (premenstrual) phase of the menstrual cycle.

PMS/PMDD is an entity that must be distinguished from (and treated differently than) anxiety disorders and depression. However, the research is still in its infancy. According to Dr. Mortola, the realization of the effectiveness of certain new drugs such as the GnRH analogs combined with estrogen/progestin replacement therapy is an important area for future research, where the optimal dosages of replacement therapy have yet to be determined. This is similar to the situation with perimenopausal HRT.

Therapeutic treatment of PMDD requires to ascertain whether the symptoms are unique to the premenstrual (post-ovulation) phase or not. This is to differentiate PMDD from clinical depression, for proper treatment. Current medical practice (both primary care and particularly psychiatry, which steps in afterward in some of the difficult cases) utilizes nothing better than the discredited calendar-based rhythm method rather than a rigorous technique for ovulation detection.

Needed: Differential diagnosis

Effective medical help for female patients requires differential diagnosis, for which the recorded symptoms must be correlated with the progress of the menstrual cycle (folliculogenesis). This correlation has not been available up to now and the diagnostician can only guess at how the scores of symptoms relate to the course of the menstrual cycle (folliculogenesis).

Differential diagnosis is essential because a clinical study found that more than 75% of patients presenting with the complaints of PMS had another condition that either could account for the symptoms or that required correction before an accurate diagnosis of PMS could be made [Mortola, JF: “Issues in the diagnosis and research of premenstrual syndrome”, Clin. Obstet. Gynecol. 35:587-598, 1992].

The physician user of our OvulographTM technology will have the benefit of working with accurate and comprehensive data on each patient’s menstrual cycle history, and will be in a better position to provide effective help.

How OvulographTM will help

Two examples of ovulographic correlation of symptoms (symptometric data, here the COPE scores) and folliculogenesis (Ovulona probe readings) can be seen below and – along with the answer to What is the meaning of symptometric data – in the document on the accompanying Page “What is symptometric?” at https://biozhena.wordpress.com/what-is-symptometric/.

Ovulographic correlation of folliculogenesis and symptometric data – click to open a clear PDF version of the image

Ovulographic Correlation of Folliculogenesis and Symptometric Data

In the first example, the cumulative COPE score rises on day 13, which is 3 days before ovulation (day 16), and we note that this is a case of an irregular cycle with a delayed ovulation. In the second example, the COPE score rises on day 17, which is 2 days after the day of ovulation (day 15).

We observe that, in the first example, in the absence of the Ovulona probe data, the “traditional” method of counting back 14 days from the first day of menstrual bleeding (namely, to day 12) would lead to the wrong conclusion that the score rise on day 13 is post-ovulatory.

Only the second example (documented post-ovulation rise of the COPE score) appears to be a case of PMS.

“Psychiatric instruments” will become women’s healthcare tools

COPE score refers to the well known “psychiatric instrument”, the Calendar of Premenstrual Experiences (COPE), described in a paper by Beck LE, Gevirtz R, Mortola JF: “The predictive value of psychosocial stress on symptom severity in premenstrual syndrome”, Psychosom. Med. 52:536, 1990.

The bioZhena technology should have a positive effect in the PMS/PMDD arena.

Two key words are pertinent in this context, namely psychoneuroendocrinology (or even psycho-neuro-immuno-endocrinology) and the much shorter psychosomatic, as in psychosomatic medicine.

See also “On the importance of symptometric monitoring” https://biozhena.wordpress.com/about/about-biozhena-tech-pitch/importance-of-symptometry/ .

Fetal sex pre-selection – the fundamentals

December 15, 2007

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

December 15, 2007

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

December 14, 2007

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.

 

BIOZHENA’S MISSION: A HEALTH TOOL FOR EVERY WOMAN

December 10, 2007

Far more than a tool to aid achieving and avoiding pregnancy

In the early years of the project, I published here a modestly formulated version of bioZhena’s vision statement. That was before a female OBGYN physician joined the team and together we broadened the vision and mission.

With the “Ambassador for the Vagina” it became plausible to fully explore the broad applicability of the technology, and to plan pregnancy monitoring and the transformation of the daily-inserted Ovulona into the semi-permanently worn telemetric cervical ring version that Kim the OBGYN named the Halo™.

Friendly Technology - with cervical ring & Ovulograph

For healthcare providers the Ovulograph™, and the Halo™ cervical ring for all women

Our vision is to create a product that practically every woman will want to use. The woman of the 21st century is envisaged to become accustomed to using her daily Ovulona and/or Halo self-check about as routinely as she is using her toothbrush.

It is pertinent to note that a May 2017 Human Factors in Computing Systems study found that the smartphone apps that track menstrual cycles “often disappoint users with a lack of accuracy… and an emphasis on pink and flowery form over function and customization”. Significantly, too, “teenage girls were relying on smartphone apps as their primary form of birth control”. Such evidence indicates that the market is primed for the bioZhena technology breakthrough.

The Ovulona™/Halo™ will be useful to the point of becoming an essential tool of women’s health management, both at home and, when appropriate, via the Ovulograph™, for the provider in the doctor’s office – and for the payer, too. Accordingly, the Ovulona will be supremely user-friendly and affordable for everyone.

See and listen to the slides in the link at the end of the post.

The Ovulona personal fertility status self-diagnosis device

 What is folliculogenesis - like EKG

Applications of cervical sensor girl w. device and other solutions - panorama1

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Fetal sex preselection – illustrated

December 3, 2007

Ovulona and logo

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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3-day window data from a study by John France et al.
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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 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.


The Alphabet of bioZhena — Abeceda bioŽeny

November 28, 2007

THE ALPHABET OF BIOZHENA WITH CLICKABLE TABLE OF CONTENTS

The Alphabet of bioZhena

A glossary of biomedical terms for bioZhena Corporation

Ovulona and logo

The glossary-and-primer of bioZhena is attached; click on one of the links above.

The glossary is just that! For more details with illustrations and more substantial treatment of certain topics, please go to the the blog, starting perhaps with the Table of Contents . Or try one of the two About pages – one about the blogger and the issues covered here , and the other About bioZhena – tech pitch . See if both these pages include the link to a quick pictorial summary of the bioZhena project, called Tweetroducing bioZhena in 8 slides !

In THE ALPHABET we expand on – and explain the meaning of – the one brief sentence: We have invented the new technology of ovulography™, fundamental to women’s health and lifestyle.

Ovulography is bioZhena’s proprietary technology for monitoring folliculogenesis in vivo. To tell the woman user, which are the three days when she can become pregnant (and the rest of the month when she cannot). And there is more, much more, which is what THE ALPHABET OF BIOZHENA is about. As is the whole of bioZhena’s Weblog .

This glossary/primer of bioZhena Corporation is no Alphabet of Ben Sira — an anonymous work, which has been dated anywhere from the seventh to the eleventh century, and which tells the story of the conception, birth, and early education of the prophet Ben Sira.

There were twenty-two stories (mimicking the twenty-two letters of the Hebrew alphabet) to answer the questions posed by the Babylonian king Nebuchadnezzar. Apart from being notable for the story of Lilith, the primordial first wife of Adam, what makes this ancient text particularly unique and fascinating is its irreverent tone …And, we get to learn of the angels who are in charge of medicine: Snvi, Snsvi, and Smnglof!

For more information on the ancient and irreverent Alphabet of Ben Sira, go to http://www.google.com/search?q=Alphabet%20of%20Ben%20Sira !

Lilith from Michelangelo’s The Temptation of Adam and Eve

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And now, as the ancients would say, remotum joco (roughly, “joking aside”):

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A simple description and pictorial representation of the female reproductive organs is available at the American Medical Association’s web site “Atlas of the Body: Female Reproductive Organs”: http://www.medem.com/MedLb/article_detaillb.cfm?article_ID=ZZZ8QKJ56JC&sub_cat=2

A more detailed treatment of Sexual Reproduction in Humans is given in http://www.ultranet.com/~jkimball/BiologyPages/S/Sexual_Reproduction.html

For a particularly enjoyable, stimulating and informative source on the intimate geography of womanhood, reach for Natalie Angier’s Pulitzer Prize winning book “Woman – An Intimate Geography”, Houghton Mifflin Company, 1999, ISBN 0-395-69130-3. An excellent background read for the appreciation of bioZhena. But read Mysterious conceptions, under M.

For all that, go to one of the attached files: The Alphabet of bioZhena in PDF format. THE ALPHABET OF BIOZHENA WITH CLICKABLE TABLE OF CONTENTS is more convenient than the PDF version that does not have the clickable table of contents.


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