An Australian study published in the New England Journal of Medicine finds Assisted Reproduction Technologies (ART) substantially increase birth defect risks.
"The unadjusted risk of any birth defect in pregnancies involving assisted conception was 8.3% (513 defects), compared with 5.8% for pregnancies not involving assisted conception (17,546 defects)," Associate Professor Davies says.
"The risk of birth defects for IVF was 7.2% (165 birth defects); and the rate for ICSI was higher at 9.9% (139 defects).
"A history of infertility, either with or without assisted conception, was also significantly associated with birth defects. While factors associated with the causes of infertility explained the excess risk associated with IVF, the increased risk for a number of other treatments could not readily be explained by patient factors. ICSI, for instance, had a 57% increase in the odds of major defect, although the absolute size of the risk remained relatively small," he says.
Of course the researchers tried to adjust for other causes of defects. For example, older women have greater risks of birth defects even without using ART. But note that since we do not all age at the same rate the women who need ART in order to conceive probably have effectively older reproductive tracts than other women at the same age who are still fertile.
But use of cryopreservation is associated with a reduction in risk of birth defects.
Associate Professor Davies says cryopreservation (freezing) of embryos was associated with a substantially reduced risk of birth defects, particularly for ICSI. "This may be due to developmentally compromised embryos failing to survive the freeze/thaw process," he says.
That's encouraging because it suggests better technologies for embryo selection could lower the rate of birth defects.
A drug that stimulates ovulation raises birth defect risks.
Also of concern was the tripling of risk in women using clomiphene citrate to stimulate ovulation outside of a closely supervised clinical setting.
I expect ART will eventually advance to the point where it will enable lower rates of birth defects than occur naturally. This will happen a few ways:
Note that even for younger women smarter embryo selection will some day make the use of assisted reproduction technologies preferable to the natural way to start pregnancies. ART will lower birth defect rates while also providing the ability to select for embryos that have desired combinations of genetic traits from the two (or more) genetic parents.
It may be possible for young women to have oocyte precursor cells removed from ovaries while young for use to create eggs to start pregnancies when they reach their 30s and 40s.
For the first time, Massachusetts General Hospital (MGH) researchers have isolated egg-producing stem cells from the ovaries of reproductive age women and shown these cells can produce what appear to be normal egg cells or oocytes. In the March issue of Nature Medicine, the team from the Vincent Center for Reproductive Biology at MGH reports the latest follow-up study to their now-landmark 2004 Nature paper that first suggested female mammals continue producing egg cells into adulthood.
"The primary objective of the current study was to prove that oocyte-producing stem cells do in fact exist in the ovaries of women during reproductive life, which we feel this study demonstrates very clearly," says Jonathan Tilly, PhD, director of the Vincent Center for Reproductive Biology in the MGH Vincent Department of Obstetrics and Gynecology, who led the study. "The discovery of oocyte precursor cells in adult human ovaries, coupled with the fact that these cells share the same characteristic features of their mouse counterparts that produce fully functional eggs, opens the door for development of unprecedented technologies to overcome infertility in women and perhaps even delay the timing of ovarian failure."
Imagine a 20 year old woman getting oocyte precursor cells extracted from her ovaries for use when she's in her late 30s or 40s to create viable eggs once her ovary eggs are all too old to start a pregnancy.
What I wonder: Does it make sense for young people to have tissue samples taken from various parts of their bodies and frozen for later use? Decades later when degenerative diseases become a problem the frozen cells might be useful for creating therapies. Access to genetically compatible yet young cells (long telomeres, little accumulated DNA damage) might provide a useful starting point to grow stem cells and other cells for therapeutic purposes.
Tissue extraction for later therapeutic use might make more sense today for the middle aged. 50 years from now biotech that can start with aged cells and create youthful cells might be quite mature. But 20 years from now cells taken from a 70 year old to create a cell therapy for that person might perform poorly.
What I'm curious to know: For, say, 75 year olds just what percentage of the cells in their bodies have substantial DNA damage? If one needed to start with cells from a 75 year old body in order to create stem cell lines for cell therapies how many cells would one need to sort through to find cells that would make good starting points for growth of therapeutic cell lines?
In theory doctors could remove, say, 100 cells, each from different parts of your body, separate them into different locations, and grow up a different cell line from each of the 100 starting cells. Well, if DNA were then removed from part of each cell line and tested (or even sequenced) what percentage of the cells would show major genetic abnormalities? How hard is it to find good starting cells in old bodies to create rejuvenating therapies?
Conscious of their aging ovaries more women are having their eggs flash frozen for later use with in vitro fertilization (IVF) to make babies.
In a Manhattan office building on a recent evening, two dozen women — all in their 30s and 40s — sit in folding chairs, balancing cellphones and glasses of wine. They're gathered for a seminar called "Take Control of Your Fertility."
Dr. Alan Copperman of Reproductive Medicine Associates of New York wastes no time laying out this harsh reality: By the time a woman hits her 40s, 90 percent of her eggs are abnormal. The chances of a typical 40-year-old getting pregnant in any given month? Ten percent. Unless, that is, she gets pregnant with her younger eggs — eggs she had frozen years before.
Many 40-year-old women are already effectively infertile. The earlier the eggs get frozen the better.
"These days we've sort of cracked the code on egg freezing and the pregnancy rates really are essentially the same as with fresh eggs now," Dr. William Schoolcraft with the Colorado Center for Reproductive Medicine said.
Want to freeze some of your eggs for when you get older? A Denver Colorado news site puts the cost at about $12,000 to $15,000.
While egg freezing probably makes sense in the 10 to 15 year time frame it won't always be necessary. At some point it will become possible to take adult cells and convert them into eggs in a lab environment. Once that capability is well developed older women will be able get a small tissue sample converted into eggs.
That loud ticking clock of an aging reproductive tract in women can be muffled by freezing an ovary at age 19 to reimplant to make babies after age 40.
Dr Sherman Silber told the American Society for Reproductive Medicine meeting in Denver a woman could freeze her ovary at 19 to use when she was 40.
Dr Silber, who says the procedure would work better than egg freezing, did the first full ovary transplant in 2007.
Any doctors reading this: Will removing just one ovary place a heavier pressure on the other ovary? Will menopause come sooner with less total ovary mass present to keep up the monthly cycle? Also, once the frozen ovary is reimplanted will menopause come later?
He said of his present clients: "These women all come to us aged 35 or 38 after they've broken up with their boyfriend of 10 years and they are worried about the future." Women should think about it earlier when they have more, better quality eggs.
Doctor Silber says with an ovary safely frozen women could take a more relaxed view of their eventual motherhood.
My guess is few women will take Dr. Silber's advice. But on the bright side: A 19 year old today will turn 40 around the year 2031. Organ growth biotechnologies might be sufficiently advanced to grow replacement ovaries by then. Sound far fetched? Anthony Atala of the Wake Forest Institute for Regenerative Medicine leads a team which is the first to implant laboratory-grown organs (bladders) into humans. Check out Atala's TED talk on regenerative medicine and the future of laboratory-grown organs.
Growth of replacement ovaries offers a number of advantages over freezing ovaries. First off, you do not need to undergo surgery when young to remove an ovary. Second, aging organs are at increasing risk of cancer. The accumulation of mutations that lead to cancers occur over decades. Replacing your ovaries (or pancreas or liver or kidneys) at age 40 would set back the age of the organs to a much earlier, less mutated, and therefore less risky stage.
To grow replacement organs that have a much lower chance of becoming cancerous requires excellent genetic testing to identify starter cell lines that do not have any mutations that boost cancer risk. Note that genetic testing is not just about your genetic inheritance or family tree (though it is great for that). Genetic testing is also a key component of strategies for regenerative medicine.
Two women taking part in the world's first controlled study of a comprehensive genetic screening test before IVF have given birth to healthy babies. The babies, twin girls born in Germany in June and a singleton boy born in Italy in September, are the first deliveries in a pilot study of comparative genomic hybridisation (CGH) by microarray, a new method of screening oocytes for IVF for a full range of chromosomal disorders.
Dr Cristina Magli, embryologist at the SISMER Centre in Bologna, one of the two centres taking part in the trial, said: " All the babies and their mothers are doing very well in terms of weight and overall developmental performance."
One goal here is to increase the rate of successful pregnancies when doing in vitro fertilization (IVF). But continued improvement in embryo selection techniques inevitably will lead to healthier babies since some flaws that aren't bad enough to cause miscarriage will also be avoided. Big strides in embryo selection will very likely eventually lead to healthier babies via IVF than via natural sexual reproduction.
Once the stage is reached where IVF is safer then starting a pregnancy in the lab will become preferred by a substantial percentage of the population. What comes next? Selection of embryos for a larger list of reasons having to do with physical appearances, athletic ability, intelligence, personality, and other attributes.
The births, as well as several ongoing pregnancies in the study group, are the final stage in the "proof of principle" that the screening of oocytes and embryos before transfer in IVF can increase birth rates; both these pregnancies were derived from oocytes whose complete chromosomal status had been assessed by microarray CGH.
The study, which was conducted in Bologna, Italy, and Bonn, Germany, was designed and organised by a task force of ESHRE to determine the clinical value of CGH as a non-subjective means of genetic screening before embryo transfer.
A substantial fraction of all embryos miscarry in humans.
Another recent report on techniques for identifying healthy embryos shows that while most human embryos fail to reach the blastocyst stage it is possible to predict which ones will succeed.
STANFORD, Calif. — Two-thirds of all human embryos fail to develop successfully. Now, in a new study, researchers at the Stanford University School of Medicine have shown that they can predict with 93 percent certainty which fertilized eggs will make it to a critical developmental milestone and which will stall and die. The findings are important to the understanding of the fundamentals of human development at the earliest stages, which have largely remained a mystery despite the attention given to human embryonic stem cell research.
A much higher percentage of human embryos fail to reach blastocyst stage. Lots of silent failures of conceptions to fail to turn into detectable pregnancies. If life begins at conception then most humans die undetected.
"In mice, about 80 to 90 percent of embryos develop to the blastocyst stage. In humans, it's about 30 percent," said Reijo Pera. "In addition, about one in 100 mouse embryos are chromosomally abnormal, versus about seven out of 10 human embryos. That's why human studies like these are so important. Women, their families and their physicians want to increase the chances of having one healthy baby and avoid high-risk pregnancies, miscarriages or other adverse maternal and fetal outcomes. It's truly a women's health issue that affects the broader family."
Why the higher rate of chromosome abnormality in human embryos? Does this happen as a result of some complex method of checking by the cells about whether they have good genetic integrity? There's a much bigger investment by parents in a human's development than is the case with mice. So tossing out questionable embryos at a very early stage of development reduces the costs of poor investments.
I see two parallel threads of biotechnological advance that will spur a shift toward IVF as the preferred method for starting human pregnancies: A) Better ways to detect defects in IVF embryos to the point where IVF becomes the safer choice; and B) knowledge derived from cheap genetic sequencing that will identify the significance of most genetic variants. Once IVF becomes safer and it becomes a way to select for desired genetic traits IVF will become the preferred way to start pregnancies, especially for the most ambitious parents.
Children conceived by in vitro fertilization (IVF) perform at least as well as their peers on academic tests at all ages from grade 3 to 12, according to a new University of Iowa study.
I would expect IVF users to be more educated and affluent than non-users of IVF on average. IVF costs thousands to tens of thousands of dollars. Also, IVF is used more by older parents. Well, education delays reproduction and increases the odds that IVF will be needed. So smarter people are more likely to need IVF to start pregnancies. One would expect their kids to be smarter on average - at least if IVF isn't lowering their intelligence enough to counteract the beneficial effects of smarter parents disproportionally using IVF.
It is not clear whether these researchers tried to adjust for parental educational attainment or income. Doesn't sound like it.
In fact, the study, published in the October issue of the journal Human Reproduction, found that children who were conceived by IVF actually scored better than age- and gender-matched peers on the Iowa Test of Basic Skills and the Iowa Test for Educational Development (ITBS/ED).
"Our findings are reassuring for clinicians and patients as they suggest that being conceived through IVF does not have any detrimental effects on a child's intelligence or cognitive development," said lead study author Bradley Van Voorhis, M.D., UI professor of obstetrics and gynecology and director of the Center for Advanced Reproductive Care at UI Hospitals and Clinics.
To investigate whether being conceived by IVF had long-term negative effects on children's cognitive development, Van Voorhis and colleagues compared the academic performance of 423 Iowa children, ages 8 to 17, who were conceived by IVF at UI Hospitals and Clinics with the performance of 372 age- and gender-matched peers from the same Iowa schools. The researchers also analyzed whether different characteristics of the children, parents or IVF methods affected children's test scores.
The IVF kids performed better than the chosen peers.
The study found that children born by IVF performed above average on standardized tests compared to their peers, and that a number of factors were linked to higher test scores, including older age of the mother, higher education levels of both parents and lower levels of divorce.
With Robert Plomin's recent progress in his search for IQ genes we are getting closer to the day when IVF embryo selection will be done to boost intelligence of offspring. Once IVF with embryo selection guided by genetic tests becomes a useful way to boost average offspring intelligence I expect we will see a huge shift toward use of IVF to start pregnancies. Even millions of women who have no problem conceiving naturally will opt for IVF in order to get offspring who are smarter, better looking, and healthier all around.
A 42% higher rate of childhood cancers among children conceived using In Vitro Fertilization (IVF). But in absolute terms the number of cancers was still very low. 15 more cancers out of 26,000 is 1 in 1733.
Swedish researchers used records of more than 26,000 children born after IVF treatment and linked them to registers of cancer diagnosis.
They found 53 children developed cancer, ranging from a very young age, up to 19-years-old, against an expected number of 38.
The team said this meant there was a 42 per cent increased risk of childhood cancer in these children.
The researchers do not know whether the IVF boosts cancer risk, It could be that women who have fertility problems might have wombs that alter development in ways that boost cancer risk. Or their eggs could have more problems than eggs of women who do not have fertility problems. Women using IVF are also older on average than women who are getting pregnant without use of IVF. More here.
The more troubling question: Do children who have higher risk of childhood cancer also have a similar higher risk of cancer in late middle are and old age? If IVF turns out to produce even a 10% increase in likelihood of cancers is one's 60s, 70s, and 80s that would come on top of a much higher base cancer rate.
For someone pondering IVF now higher rates of birth defects when using IVF also need to be taken into consideration.
Improving technologies for embryo testing and selection should go at least part of the way toward closing the risk gap between naturally started pregnancies and IVF pregnancies. While existing embryo genetic testing technologies might pose a risk to embryos in the long run I expect IVF conception to become lower risk than natural conception as IVF combined with advances in embryo genetic testing (more here) will enable a lowering of birth defect rates below the rates of birth defects seen with naturally started pregnancies.
The rapidly declining cost of full genome genetic sequencing technology is about to produce a flood of genetic data that will lead to the identification of what a large number of genetic variants mean. These findings will increase the value of IVF embryo testing as prospective parents gain the ability to select physical and mental traits of their future offspring by choosing which among several embryos to implant.
Rome, Italy: Researchers have developed a way of accurately predicting when women will hit the menopause using a simple blood test. The average difference between the predicted age and the actual age that the women in their study reached the menopause was only a third of a year, and the maximum margin of error was between three and four years.
Dr Fahimeh Ramezani Tehrani will tell the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome today (Monday) that her findings have implications for women and their doctors; if the results of the research are supported by larger studies, it means that women will be able to discover early on in their reproductive life what their expected age at menopause will be, so that they can plan when to start a family.
By taking blood samples from 266 women, aged 20-49, who had been enrolled in the much larger Tehran Lipid and Glucose Study, Dr Ramezani Tehrani and her colleagues were able to measure the concentrations of a hormone that is produced by cells in women's ovaries – anti-Mullerian Hormone (AMH). AMH controls the development of follicles in the ovaries, from which oocytes (eggs) develop and it has been suggested that AMH could be used for measuring ovarian function. The researchers took two further blood samples at three yearly intervals, and they also collected information on the women's socioeconomic background and reproductive history. In addition, the women had physical examinations every three years. The Tehran Lipid and Glucose Study is a prospective study that started in 1998 and is still continuing.
Such a predictive capability certainly is useful for women who want to know when they'll lose their fertility. But it has additional uses in the study of the aging process. Methods for measuring rates of aging are useful because they enable researchers to much more rapidly check whether drugs, diet, and other measures to slow aging are actually providing any benefit. For example, drugs that might slow ovary aging could be tested for their effects on blood AMH levels.
A 20 year old who is going to experience early onset of menopause could be warned 15 to 20 years in advance.
"The results from our study could enable us to make a more realistic assessment of women's reproductive status many years before they reach menopause. For example, if a 20-year-old woman has a concentration of serum AMH of 2.8 ng/ml [nanograms per millilitre], we estimate that she will become menopausal between 35-38 years old. To the best of our knowledge this is the first prediction of age at menopause that has resulted from a population-based cohort study. We believe that our estimates of ages at menopause based on AMH levels are of sufficient validity to guide medical practitioners in their day-to-day practice, so that they can help women with their family planning."
Another advantage of being able to detect some aging or disease outcome decades in advance: One can study the diet and lifestyle of people decades before the change or disease manifests and one does not have to guess what happened decades previously that might or might not have contributed to the outcome.
Gene expression could also be studied in younger women to look for differences in patterns in gene expression and also in genetic sequences to try to pin down a genetic cause that plays out over decades.
Researchers at Newcastle University in England have moved the nucleus of a fertilized egg to a different egg in order to avoid mitochondrial DNA diseases.
Researchers have successfully transplanted the genetic material in the nucleus of a fertilized human egg into another fertilized egg, without carrying over mitochondria, the energy-producing structures of the cell. The technique could be used to prevent babies from inheriting diseases caused by mutations in the DNA of mitochondria, which are present in the cytoplasm of the egg.
The researchers haven't yet been given permission to try this procedure to start a real pregnancy. Would US fertility clinics need to ask permission to try this technique to start a pregnancy? Reproductive technologies are much less regulated in the United States.
The mitochondria are sort of like cells within our cells which specialize in generationg energy. Mitochondria have their own small piece of DNA (less than 15,000 DNA letters) that code for several genes involved in breaking down sugar to create chemical energy. Some people carry harmful mutations in their mitochondrial DNA.
A baby created by this technique would end up with DNA from 3 different people. The nuclear DNA would come from the two parents, But the mitochondrial DNA would come from an egg donor.
Things will start to get really interesting when it becomes possible to choose individual chromosomes to put into an egg. Combine that capability with cheap DNA sequencing and suddenly a huge leap in parental control over offspring genetic inheritance will cause an amazing acceleration in the rate of human evolution.
Genetics & IVF Institute (GIVF) is launching a Personal Egg Banking service in the Washington, DC area to help women 40 and under who want to cryopreserve (freeze) their eggs now for use in the future when they wish to become pregnant. The age of a woman's eggs dramatically affects her ability to conceive. At 30, a healthy woman has about a 20% chance per month of conceiving, but the likelihood of pregnancy plummets as a woman grows older. At 40, her chances drop to about 5%.
Egg banking is one of those services where the buyers will tend to wait too long before admitting they need the service. A woman in her late teens is probably the ideal candidate to bank some eggs due to her still having very youthful eggs. But most women that age who eventually want children do not want to think about the possibility that they won't have all their dreams come true in a timely manner.
Women spend so much time pursuing their careers that many are infertile by the time they get around to trying to start a family.
"Many patients with age-related infertility are very distressed because they did not fully understand how difficult it would be to conceive at an older age," says Dr. Lawrence Udoff, a reproductive endocrinologist at GIVF. "Some of these women weren't ready to have a child when they were younger because they had not found a partner or they were immersed in their careers. Now that they are ready, they are facing age-related infertility."
I would be very curious to know the average age of a woman who uses an egg banking service.
Perhaps medical tests will alert women about declining fertility a few years before the infertility risk becomes high. Then women would know to go and get some eggs banked.
New technology has arrived in Australian IVF clinics that will, for the first time, enable any woman to establish quickly and easily - and for only $65 - whether she has a decent chance of natural conception.
The test - tagged the "egg-timer" - measures the hormonal concentration in her lower plumbing regions.
It will reveal whether any of the one million eggs that she was born with are still quietly hibernating in there and how many of them are already hard-boiled.
If such testing becomes cheap and easy to do women could get periodic tests of the trend in their fertility level.
Counsyl, a Stanford startup based in Redwood City, CA, has developed a genetic test for prospective parents that determines their risk for passing more than 100 different genetic diseases on to their child. The test, which costs $349 and is already covered by some major insurers, could rapidly expand preconception screening for rare inherited conditions.
You can bet that the list of testable genetic diseases will grow each year and the general usefulness of pre-pregnancy genetic screening will grow along with the list of testable genes.
The big recent cost declines for genetic testing and genetic sequencing don't just make a test such as this cheaper. Lower costs also enable scientists to engage in much larger scale searches for biologically significant genetic variants. As a result the number of known ways that genetic variants cause human differences is going to grow by orders of magnitude in the next 10 years.
Most (all?) of these genetic variants mentioned above only cause disease if inherited from both parents. Test results for a couple can influence their decision on whether to start a pregnancy naturally or via IVF with pre-implantation genetic diagnosis or whether to avoid reproduction entirely. If you are thinking about making a baby then $349 to assess your genetic risks seems like a small price to pay as compared to the total costs (which can run into the hundreds of thousands of dollars) to raise a child to adulthood.
Looking down the line 10 or 20 years I expect to see online dating services match people up based on avoidance of shared harmful recessive genes. Searchers for Mr. and Mrs. Right will get steered toward prospective mates with whom they can pretty safely make babies.
A successful collaboration between the Universities of St Andrews and Edinburgh has resulted in a better understanding of how many eggs a woman has in her ovaries (ovarian reserve) from conception to menopause. It is the first time that scientists have ever modelled human ovarian reserve from establishment before birth to menopause around 50 years of age.
By age 40 only 3% remain. The odds of a successful pregnancy at that point therefore are small to none.
Tom Kelsey, a Senior Research Fellow at the School of Computer Science at St Andrews, said, "Previous models have looked at the decline in ovarian reserve, but not at the dynamics of ovarian reserve from conception onwards. Our model shows that for 95% of women, by the age of 30 years, only 12% of their maximum ovarian reserve is present, and by the age of 40 years only 3% remains.
They find no evidence for stem cells that can make more eggs.
"Furthermore our model provides no evidence for the presence of stem germ cells in the ovary that could increase the number of eggs present in the ovary and delay the menopause."
Hollywood starlets having twins in their 40s are almost all using donor eggs.
Going forward the generation of new eggs from stem cells will certainly become possible some day. But when? My guess is it will even become preferable since future techniques for modifying genes in the stem cells will allow people to eliminate genetic defects and also combine the most designed genetic features from all their chromosomes (and beyond) into a single haploid egg. The same will be done with male sperm. Then the rate of human evolution will accelerate orders of magnitude over the current already fast rate of human evolution.
Methyl groups put on the backbone of DNA regulate gene expression. Some researchers find that IVF babies do not have the same pattern of DNA methylation as babies conceived using natural sex.
“These epigenetic differences have the potential to affect embyronic development and foetal growth, as well as influencing long-term patterns of gene expression associated with increased risk of many human diseases,” said Professor Carmen Sapienza, a geneticist at Temple University in Philadelphia, who jointly led the research.
People who use IVF are, on average, older than people making babies without the help assisted reproduction technologies. Plus, they have problems that prevent them from starting pregnancies naturally, The researchers can not rule out the possibility that these factors explain the difference in methylation. A much larger sample set of babies born to women of a wide range of ages might provide hints as to whether IVF is the cause. If IVF is the cause then why? Too much oxygen exposure? Or maybe the drugs used to cause egg maturation?
Assisted Reproduction Technologies (ART) keep getting better. In Vitro Fertilization (IVF) has a very bright future.
Amsterdam, The Netherlands: A new test examining chromosomes in human eggs a few hours after fertilisation can identify those that are capable of forming a healthy baby, a researcher told the 25th annual conference of the European Society of Human Reproduction and Embryology today (Monday 29 June). Dr. Elpida Fragouli, from the Department of Obstetrics and Gynaecology, University of Oxford, UK, and Reprogenetics UK, said that her team's work had already enabled seven ongoing pregnancies in a group of older women with a history of multiple failed IVF attempts.
I would not be surprised if some women in their late 30s go traveling between continents to go to Oxford to get access to this method of embryo selection.
"Out of 35 patients who had embryo transfers after the test, we achieved a pregnancy rate of 20%, which is exceptional considering the extremely poor prognosis of the women involved." she said. "This represents a doubling of the usual pregnancy rate for women who fall into this category, which is otherwise, at best, under 10% and, at worst, zero. To date, we have two live births from this group, and all the other women who became pregnant have maintained their pregnancies. The study is continuing, and we believe that we will achieve more pregnancies with the help of this technology in the future."
The scientists used the Comparative Genomic Hybridisation (CGH) technique to count the chromosomes in each egg. Unlike conventional screening strategies, using the fluorescent in situ hybridisation (FISH) method, which allows less than half of the chromosomes of an embryonic cell to be examined, CGH enables the evaluation of the entire chromosome complement. CGH was used to examine the fertilised eggs by looking at polar bodies, tiny cells that are a by-product of egg development. The chromosomes of polar bodies provide an indication of whether the corresponding egg is normal or abnormal; if the polar bodies have the wrong number of chromosomes, so does the egg.
Better tech for doing IVF embryo testing will make IVF more appealing as a way to create babies as compared to plain old-fashioned sex. We'll still have sex. It just won't be for making babies. Cheap genetic testing which yields lots of details about embryo genetic profiles will cause people to personally practice eugenics on a massive scale and the great human evolution acceleration of the last 10,000 years will pale next to the massive human evolution of the next 100 years.
At some point I expect IVF baby creation to become less risky than conventional sex as a way to start pregnancies that turn out well. That point is probably approaching in the next 10 years. Granted, women in their late 30s starting pregnancies will still run bigger risks of bad outcomes as compared to women in their early 20s. But the total risk will go down for all women using IVF and eventually genetic testing of embryos will become so powerful that IVF will yield smarter, healthier, better looking, and otherwise - dare I say it? - superior babies. Yes, I dare.
Assisted reproductive technology (ART) is responsible for an estimated 219,000 to 246,000 babies born each year worldwide according to an international study. The study also finds that the number of ART procedures is growing steadily: in just two years (from 2000 to 2002) ART activity increased by more than 25%.
The study, which is published online today (Thursday 28 May) in Europe's leading reproductive medicine journal Human Reproduction , gives figures and estimates for the year 2002, the most recent year for which world figures are available. A total of 1563 clinics in 53 countries provided data for the report, but data were missing from several other countries, mostly in Asia, Africa, Oceania and the West Indies. The authors estimated that these missing countries probably performed between 10-20% of ART procedures, and they took this into account when they calculated the total number of ART babies born worldwide.
So far the use of ART is mainly used by people who can't otherwise start a pregnancy. However, advances in genetic testing tech will eventually make ART far more mainstream. When it becomes possible to use genetic testing to choose features for offspring I predict that egg fertilization in laboratories will become the preferred way for upper classes to start pregnancies. The ability to choose embryos based on criteria like intelligence, personality, health and physical attractiveness will make old fashion sex obsolete for making babies.
Michèle Hansen, a researcher and PhD student at the Telethon Institute for Child Health Research in Western Australia, said: "We found that twins conceived following ART treatment had a greater risk of adverse perinatal outcome, including preterm birth, low birthweight and death, compared with spontaneously conceived twins of unlike sex. ART twins had more than double the risk of perinatal death compared to ULS SC twins, although the risk was similar to that of all SC twins, including identical twins.
"ART twins stayed longer in hospital than ULS SC twins at the time of their birth: an average of 12 days compared with eight days. ART twins were four times more likely to be admitted to neo-natal intensive care than ULS SC twins, and were more likely to be admitted to hospital during the first three years of their life. After adjusting for confounding factors such as year of birth, maternal age, parity and so on, ART twins still had a nearly two-thirds higher risk of being admitted to neo-natal intensive care, and a higher risk of being admitted to hospital in their first three years of life, although this was only statistically significant in their second year, when their risk was nearly two-thirds higher."
Ms Hansen continued: "Couples undergoing fertility treatment should be aware that, in addition to the known increased perinatal risks associated with a twin birth, ART twins are more likely than spontaneously conceived twins to be admitted to neonatal intensive care and to be hospitalised in their first three years of life.
These results are an argument against implanting multiple embryos when doing in vitro fertilization (IVF). But many women opt for multiple embryo implants because they want to increase their chances of starting even a single pregnancy. Women in their mid 30s and later already hear a lot clock ticking and realize that time is not on their side. So rather than undergo a series of single embryo implantations they get more than one embryo implanted at once.
Development of better ways to test embryos to identify better embryos for implantation increase IVF success rates. These methods that boost success rates decrease the need for multiple embryo implantation. Also, better testing (genetic and otherwise) will identify embryos that have much lower odds of producing birth defects. So in time IVF combined with pre-implantation testing could become safer than pregnancies started the natural way
A British guy suffering from leukemia had his sperm stored 22 years ago and his sperm produced a baby 22 years later - a new record.
Chris Biblis was 16 when doctors told him that he needed radiotherapy that would leave him sterile and recommended before going ahead with the life-saving treatment that they put a sample of his sperm into cryogenic storage for future use.
Now aged 38, he is celebrating the birth of a healthy baby daughter, Stella, who was conceived after scientists injected a defrosted sperm into an egg from his wife, Melodie, and implanted it in her uterus.
I'm thinking guys in their teens ought to get their sperm stored and girls in their teens ought to get their eggs stored.
Women wouldn't need to undergo heavy (and risky) hormone therapy to extract eggs. A technique called in vitro maturation (IVM) cuts costs and risks with IVM down to $5000 at one clinic. What I wonder: can eggs be frozen before maturation? That'd delay costs and make egg storage at a young age more affordable.
Huge banks of stored sperm and eggs would open up the possibility of much bigger and higher quality markets for sperm and eggs. Once DNA sequencing becomes cheap I expect teens will advertise for offers for their sperm and eggs by publishing their DNA sequences on web sites under pseudonyms.
The technology: Metabolomic testing reveals trace molecules remaining after an array of cellular processes. Previous studies have shown that metabolomic profiling can be used to identify unique biomarkers left behind by embryos in culture, which foretell the embryos with the highest reproductive potential in IVF. "Think of it as a sort of smog test for the embryo," said Behr. "It tells you how clean the engine is burning, and whether there are any problems."
The study: The study involved extracting eggs from 43 women, incubating them in culture for three hours and then examining their metabolomic results before fertilization. The researchers then documented what happened to each egg: Whether it was fertilized, the quality of the resulting embryo on days three and five, and whether it led to a successful pregnancy.
Publication: The study appeared in the February issue of Reproductive Biomedicine Online. Behr is the senior author; Jennifer Dasig, an embryologist at Stanford, is one of the co-authors.
The findings: The researchers established a correlation between the number of particular trace elements left behind by the eggs and both embryo viability and pregnancy rates. "This shows we can predict embryo development and viability from the egg," said Behr.
Why does this matter? Unless you are the (foolish) Octomom you probably don't want to give birth to multiple babies. The greater the number of fetuses in the womb the smaller each will be, the more likelihood of birth complications (e.g. premature birth) and the lower the intellectual level and health of resulting fully grown children.
The problem with in vitro fertilization (IVF) is that women who try IVF want to start a pregnancy but don't know how many embryos they need to succeed. Their biological clock is ticking and many are in their 30s with declining fertility. Their eggs and wombs are aging. Methods that more accurately identify which of several embryos to implant will increase success rates while simultaneously reducing multiple birth pregnancies. This is a double win.
In vitro maturation (IVM) is a variation on conventional in vitro fertilization (IVF) where no hormones are administered to a woman to mature eggs before removal. IVM has yielded lower success rates as compared to IVF. But advances in IVM technique have raised IVM success rates for assisted reproduction.
A form of IVF that does not require women to take powerful drugs has a success rate similar to conventional IVF, according to data from the only UK fertility clinic licensed to carry out the treatment.
The team at the Oxford Fertility Unit followed 40 women who received the treatment known as in vitro maturation – including those who had the first babies born in Britain using the technique in October last year. Nine of the women became pregnant – a pregnancy rate of 33% in under 35s.
IVF hormone treatment can cause pain, sickness, and an acute deadly complication. Plus, it might raise risks of other problems with ovaries later on. Plus, it costs more. In the future these differences will matter to to many more women than just those who have problems starting pregnancy. More powerful genetic testing techniques will make the use of assisted reproduction more popular as prospective parents try to select which genes to pass along to their offspring.
Among women under 35 - all of whom had an ovary condition that affects fertility - 48% became pregnant with IVM using their own fresh eggs and the percentage achieving a clinical pregnancy, where the baby's heart beat is detected, was 33%. This compares with a UK national average of 31% for those in the same age group having conventional IVF.
As well as being more successful, the new technique is also cheaper than the standard IVF as it largely avoids the need for drugs, which cost around £1,500 per cycle.
Historically success rates of IVM have been lower than standard IVF, at 25 per cent compared to around 36 per cent on average.
IVM avoids the risk of ovarian hyperstimulation syndrome where in some cases cysts form on the ovaries, fluid accumulates in the abdominal cavity and lungs, and function of kidneys and other organs can be compromised. IVM will probably replace IVF for the masses when many millions of women embrace genetic selection for offspring.
Also see my previous posts Lower Fertility Drug Doses Just As Effective For IVF and In Vitro Maturation Advantages Over IVF As Pregnancy Starter.
A 38-year-old woman from London has given birth to the world’s first baby conceived after a full ovary transplant.
The patient, who received an ovary donated by her identical twin sister, had a healthy daughter weighing 7lb 15oz today, delivered by Caesarean section.
The birth is the ninth reported worldwide after ovarian tissue was transplanted from one sister to another, but the first in which an entire ovary was used.
The woman who received the ovary went into menopause at age 15 for some reason. The ovary transplant is amazing. But also note the age of the woman. That the donor ovary could produce viable eggs really goes against the odds.
Dr. Sherman Silber, who carried out the ovary transplant at the Infertility Center in St. Louis Missouri, argues that young women should consider getting one of their ovaries removed and frozen for replacement when they get older.
I see no reason why this technique to prolong reproductive life should not be routine for all women who want it. The cancer patients who we have frozen ovaries for say they feel really lucky they had cancer, which is an odd thing to say. But they say 'I'm getting older and am not in a relationship and all my friends are worried about their biological clock. But I'm not worried because I've got a young ovary frozen'.
They wouldn't have done this if they were not confronted by the immediate situation of losing their fertility because of their cancer treatment but then they think about it a couple of years later and they are glad they did it because of the simple biological clock reasons.
Dr. Silber says this will extend the fertile period and also delay the symptoms of menopause.
What comes next? Once it becomes possible to grow ovaries from stem cells the logical next step will be for a woman to get some adult cells removed from her, genetically manipulated to become stem cells, and then further genetically manipulated with assorted improvements. Then the stem cells will get grown up into ovaries and implanted into her so she can have better babies than she'd have with her unenhanced genetic endowment.
Two advances in pre-implantation testing of in vitro fertilization (IVF) embryos offer advantages for higher pregnancy rates and more desired genetic features in offspring. First off, at least for some categories of women having reproductive problems a new embryo screening technique called comparative genomic hybridization (CGH) can double the rate of successful pregnancies when using IVF.
The new approach improves on this by testing IVF embryos when they reach the blastocyst stage of 100 to 150 cells. This allows extra cells to be removed for genetic analysis, giving increased accuracy.
It also employs a more advanced profiling system called comparative genomic hybridisation, which can screen all 23 pairs of chromosomes, against only ten with existing techniques.
The technique involves letting the embryos divide more times before cells are extracted for testing. Unlike in previous techniques all 23 chromosomes are tested for aneuploidy (where the wrong number of chromosomes is present rather than a pair of each chromosome type).
In the new approach the test is conducted on blastocysts, embryos grown for five days until they have 100 to 150 cells. These are larger and stronger, allowing cells to be removed more safely
So more cells are removed later and then fancier tests are done on them.
Oxford Fertility Unit has applied for a licence that would allow them to carry out sophisticated screening of embryos to look for defects which reduce the chances of them leading to a successful pregnancy.
Current techniques mean that only half of the embryo's DNA can be checked for problems before being implanted in the womb.
A new method, which is being used in America, can check 23 pairs of chromosomes, meaning many more defects can be found and those embryos discarded so only the perfect ones – with the best chance of creating a baby – are then implanted in the womb.
Analysing the embryos using the latest technique meant that all 23 had at least one normal blastocyst for transfer. A total of 50 embryos were transferred in 23 cycles.
Of the women, 21 fell pregnant (91%) and 20 (87%) had a clinical pregnancy (where a foetal heartbeat is confirmed by ultrasound).
Experts predict the live birth rate will be 78%. This compares with an anticipated 60% for the same patients without embryo screening.
Research team members Dr Mandy Katz-Jaffe at the Colorado Centre for Reproductive Medicine and Dr Dagan Wells of Oxford both think this testing technique works much better.
"The pregnancy rates we've got so far are absolutely phenomenal," said Dr Dagan Wells at Oxford University and Reprogenetics UK, who led the study. "We're ready to begin a trial in the UK, and we have a couple of licence applications in to the Human Fertilisation and Embryology Authority to start offering CGH to patients." The HFEA is the UK's regulator of fertility clinics.
Another advance in embryo genetic testing will have greater impact in the long run: Karyomapping allows checking of all known genetic conditions.
“What we’re basically doing is mapping family trees, so you can work out which parts of your chromosomes came from which grandparents,” Professor Handyside said. “This turns out to provide a truly universal method for PGD – that’s why we’re excited about it.
“At the moment, there are preimplantation tests for only a small fraction of the 15,000 genetic conditions that are known. This test is capable of detecting any of them. There is no need to find the mutation that is affecting a family, and work up a test. You do the analysis, and just read off the results.”
As the technique maps all the embryo’s chromosomes, it can check any gene, allowing several to be screened at once. It could also be used retrospectively, once an embryo has become a child, to provide wider information about its genetic inheritance.
With declining costs for genetic testing just about any genetic variation that has functional significance will be testable before embryos are implanted. Combine that testing ability with understandings of what more genetic variations mean and very suddenly we are going to reach a stage where embryo selection offers huge advantages to anyone who wants to make their offspring smarter, better looking, healthier, or possessing of any other most desired genetic features of each parent.
Once we know the meaning of enough different genetic variants the use of natural sexual relations to start pregnancies will pass out of favor for large segments of many populations. In nations where governments allow people to select embryos for reasons other than disease avoidance (and I expect the US to fall into this category) the advantages for couples who want smarter kids, kids with desired personality characteristics, kids with better looks, and other qualities will be so incredibly compelling that IVF with genetic testing will become very common very quickly. I expect it to take off first with the most educated and most affluent and ambitious.
By the year 2020 I predict at least 10% of all pregnancies in the United States will involve IVF and embryo genetic testing. Governments that restrict this testing are setting up their populations to fall behind in intelligence and other measures.
Barcelona, Spain: Children born after a frozen, thawed embryo has been replaced in the womb have higher birth weight than those born where fresh embryos were used, Danish scientists reported to the 24th annual conference of the European Society of Human Reproduction and Embryology today (Tuesday 8 July). The mothers had longer pregnancies, and the children did not show an increased risk of congenital malformations, said Dr. Anja Pinborg, from the Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
One possible explanation: freezing of the embryos somehow changes the epigenetic state of the embryos in a way that stimulates growth. I think that explanation unlikely though. The fact that the pregnancies from frozen embryos lasted longer explains at least part of the higher birth weights. But why the longer pregnancies?
The scientists studied all the 1267 children born in Denmark between 1995 and 2006 after frozen embryo replacement (FER). The children were divided into three groups; those born after cryo-preserved IVF (878), those born after cryo-preserved ICSI (310), and 79 where the method of creation of the embryos was unknown. During the same period 17857 children were born after IVF/ICSI treatment using fresh embryos, and these children were used as controls. Data on the children's outcomes, including congenital malformations, were obtained from Danish national registries.
The fact that freezing reduces the need for women to undergo additional hormonal therapies to produce more eggs suggests some other explanations. First off, a woman who receives a thawed embryo is further past the time when her body received the egg release stimulating hormones. That might make a difference in her metabolism where her body starts out the pregnancy in a less stressed out state. Maybe that allows the pregnancy to go longer.
Freezing embryos allows couples to have several cycles of IVF/ICSI from the same egg collection. The embryos are subsequently thawed and replaced three to five days after ovulation in exactly the same way as fresh embryos are used. The technique helps to reduce the number of times ovaries are stimulated and eggs collected.
The fact that the ovaries get stimulated in later attempts with the no-freeze approach might mean that the eggs from the later cycles are more tired. The eggs from the first cycle might be healthier. Again, I'm speculating.
The scientists found similar rates of multiple pregnancies in the FER groups (ICSI 11.7% and IVF 14.2%), but in the fresh embryo groups the rates were considerably higher (ICSI 24.8% and IVF 27.3%). Maternal age was significantly higher in the FER group. Pregnancy duration was significantly longer for these mothers, and birth weight was also higher – about 200 grams – in the FER group. The proportion of low birth weight FER children significantly lower, as was the percentage of pre-term births.
The frozen embryo replacement (FER) group had fewer neonatal ICU admissions.
"Additionally there were significantly fewer children admitted to a neonatal intensive care unit in the FER group," said Dr. Pinborg, "although, when limited to single births, this difference disappeared. Most encouragingly, we found no increased risk of congenital malformations in the FER group; the rate in this group was 7.1% compared to 8.8% where fresh embryos had been used."
When cheap DNA testing technologies can tell us many things about the genetic characteristics of each embryo the motivation for using frozen embryos will go down. Most prospective parents will compare the genetic profiles of a dozen embryos and decide they want one or two of them way more than the rest of them. They might still freeze the embryos not implanted on the first attempt. But if the first embryo implantation attempt does not lead to a pregnancy they'll be motivated to try to create some new embryos in hopes of getting genetic profiles more to their liking.
Frozen eggs strike me as more interesting than frozen embryos. If frozen eggs can be stored for long periods without complications their storage could become popular. A woman in late her teens will be able to freeze young eggs years before she meets Mr. Right. Then in her 30s those frozen eggs will serve as an insurance policy in case the eggs remaining in her ovaries get too old.
Frozen eggs might create a much bigger impact on future human evolution than frozen embryos because the ability to freeze eggs could create a much bigger egg donor market. Egg customers will no longer be limited to only those eggs from women willing to sell at a given moment. Similarly, sellers will be able to bank some eggs and wait for customers to come along who are willing to meet their price. A seller could bank some eggs into a repository freezer when it is convenient. A college student woman won't need to turn down a prospective customer just because it is mid-terms or finals time. Harvest the eggs after finals and they'll be available for sale for months and years to come.
As DNA testing results become more powerful egg donors with sought after genetic profiles will find that banking lots of frozen eggs very profitable. I expect top egg donor prices to rise from the current tens of thousands of dollars to hundreds of thousands of dollars. Women with the right looks, intelligence, personality, and low health risks will be able to sell egg for much more when their genetic profiles show they offer much higher odds for giving prospects parents what they want in their children.
June 20, 2008 -- One in 100 U.S. babies was conceived in a test tube -- and half these babies were twins, triplets, or higher multiple births, the CDC reports.
The CDC's most recent data on in vitro fertilization or IVF covers the year 2005. The data come from 422 of the 475 U.S. medical centers that provide various forms of assisted reproduction technology to people with fertility problems.
The trend toward greater use of IVF is driven in part by women delaying attempts to make babies until they develop their careers and achieve more financial security. But the development of better reproductive technologies is also making IVF a more attractive option.
My expectation is that improvements in IVF techniques will combine with genetic testing to make IVF highly advantageous over sexual intercourse for starting pregnancies. First off, improvements in IVF will lower costs, lower risks, and increase odds of success. Second, genetic testing will allow IVF users to choose genetic characteristics for their offspring. Once we know a great deal about the functional significance of tens and hundreds of thousands of genetic variations many will elect to use IVF combined with pre-implantation genetic testing to choose embryos that contain combinations of genetic features that people want for their children.
I expect IVF popularity to skyrocket in the next 30 years as IVF gives people a big edge in making their babies, smarter, healthier, more attractive, better behaved, and otherwise having more of the attributes that parents want their kids to have.
Evelyn Telfer of the University of Edinburgh and colleagues have developed a method to mature eggs outside of the ovary. This method avoids the need to expose a woman's body to powerful ovary-stimulating hormones.
Telfer said the new technique had several advantages over standard practices. It took just 10 days for an egg to mature using the new method, while it might take several months for an egg to mature inside the ovary, and one piece of tissue can provide many dozen eggs, rather than the 10 or so harvested during IVF. In addition, the technique would avoid the need for a woman to take hormone injections, which are needed in standard IVF to stimulate her ovaries to over-produce eggs.
The ability to grow large numbers of eggs creates the possibility of a much bigger benefit: The ability to do embryo selection over a much larger set of embryos. When DNA testing becomes cheap and revealing the ability to select among dozens of embryos for implantation will spark a huge acceleration in the rate of evolution of humanity (or of various post-humanities that will emerge). In 30 years (assuming the robots don't take over) the average baby getting born among the middle and upper classes of the more developed countries will be smarter, healthier, and better looking due to widely practiced embryo selection guided by DNA testing results.
The scientists from Edinburgh University have shown that immature eggs can be frozen, grown and matured in the lab.
The process could lead to women having pieces of ovary containing the immature eggs removed and stored. Much later on, they could be thawed, fertilised and finally implanted into the womb.
Telfer thinks this method is still 5 to 10 years away from being usable in humans.
I can see this method increasing the supply of donor eggs. More women will be willing to sell their eggs when they can do it without undergoing treatment with risky ovary stimulation drugs. The ability to freeze the ovarian tissue will allow buyers to choose among a larger set of women who had their ovarian tissue frozen over many years.
The use of this method might be short-lived as techniques to turn adult skin tissue into eggs will eventually eliminate the need to start with ovarian tissue in the first place.
Reproductive biotech company of BioXcell of Beverly Massachusetts has developed a method to enhance fertilization using a device placed inside a woman to hold both eggs and sperm.
The Invocell device is a sealed capsule that allows fertilisation to take place inside the body, in the vaginal cavity. A woman would first be given mild drugs to stimulate her ovaries, and then eggs would be removed from them while she is under sedation. Up to seven eggs are then put into the Invocell capsule, along with washed sperm. The capsule is then placed inside the vagina. After three days the patient would return for a second appointment, in which the capsule is removed and any fertilised embryos are examined for quality. The best one or two would then be transferred to the womb.
This approach cuts costs by avoiding the need for a lab where eggs get artificially inseminated and embryos grow. The woman's body serves in place of the lab but with the capsule to bring an assortment of eggs together with the sperm. The device keeps the eggs together where they can be easily found once fertilized.
A Pacific Fertility Center (PFC) patient, who underwent an embryo transfer with embryos created from vitrified and warmed donor oocytes (eggs), successfully delivered a baby in late October 2007. A healthy baby boy was born at term. Three other pregnancies are ongoing and are expected to deliver in 2008.
The key is very rapid freezing.
In recent months, the newer vitrification technology has been used at PFC for unfertilized egg preservation. Vitrification works by using higher concentrations of cryoprotectants and much faster cooling rates. Cells are cooled in tiny straws which achieve cooling rates of several thousand degrees per minute. When vitrification straws and cryoprotectants were first approved by the FDA for human embryos, PFC began the process of adapting the technology to unfertilized eggs (oocytes). "Even though we've been handling oocytes and embryos for many years, this technology provided new challenges due to the tiny size of the straws and the speed at which they had to be cooled," says Joe Conaghan, Ph.D., HCLD, Laboratory Director and Embryologist at PFC. "Once proficient with the procedure, we began to freeze high quality oocytes from donors that had proven fertility. Using these quality oocytes, we could be assured that any failure would be the result of the vitrification technology and not the oocytes."
Five oocyte donors in their twenties were recruited and all of their oocytes were vitrified immediately after their oocyte retrieval procedures. The oocytes were then offered to specific PFC patients waiting for embryo donation. The immediate availability of the vitrified oocytes and the ability to choose the sperm source made this a great alternative to accepting donated embryos.
PFC had immediate success with the first recipient. "We had vitrified 16 oocytes from the first donor. For the first recipient we warmed only 7 of these," explains Dr. Conaghan. "Four hours later we injected a single sperm into 6 oocytes that survived the vitrification process (1 oocyte had not come through the process successfully). The next morning, 3 of the oocytes had fertilized. Two days later, 3 embryos were transferred. A positive pregnancy test and ultrasound confirmed a singleton pregnancy. This success was a great reward for our efforts."
Overall, PFC had 7 out of 10 embryos implant after transfers to 6 recipients. What is very exciting is that this implantation rate (70%) is comparable to the implantation rates seen with donor oocytes which have not been cryopreserved.
This technology will expand the market for donor eggs because buyers won't be limited to choices among the cohort of women who are both currently fertile and willing to sell their eggs.
This technology will let women pursue careers for more years before finally trying to have kids.
In future a new method could help some couples who are childless against their will. The microscopic procedure significantly improves the success rate of 'ICSI' (intracytoplasmic sperm injection). This was discovered by scientists at the University of Bonn together with colleagues from China and industrial partners in a study of 124 women. Up to now, the desire to have a child is only fulfilled for every third couple that decides to have ICSI. In a study the artificial insemination method was twice as successful. The scientists have now published their data in the journal 'Reproductive BioMedicine'. (Online version available at http://www.rbmonline.com/Article/3161).
Improvements in artificial insemination technology are going to eventually move into the mainstream when genetic testing starts providing a big advantage for those who choose to start pregnancies with IVF. So you might think an advance like this one only applies to the small minority with fertility problems. But in fact this technique or others like it will eventually get used to start a large fraction of all pregnancies in developed nations.
In cases where they can identify 2 promising ova they can achieve a 50% success rate.
Which of the fertilised ova are finally implanted has usually been left up to chance. But today it is known that not all ova have the same quality. Using a special procedure the Bonn scientists can select the two most suitable candidates. 'For this we observe the ovule integument under a DIC microscope,' Dr. Montag explains. 'There it appears as a luminescent orange-red ring. The brighter this ring is and the more uniformly it shines, the greater the chance that it becomes a child.' The reason for this is that the ovule integument always seems to have a particularly uniform structure if the cell has matured under good conditions.
Normally every third ICSI is successful. But if medics used two 'good ' ova in their experiment, this rate increased to more than 50 per cent. With a 'good' and a 'bad' ovum the success rate was still around 40 per cent, using two 'bad' ones only 20 per cent. 'Mind you, two “good” ova are rare,' Markus Montag emphasises. 'Only with two out of ten cells does the ovule integument have an intense regular orange colour.'
If only 2 out of 10 IVF ova look good by this criteria that makes genetically-based embyro selection harder to do. Ideally one would want to be able to choose among dozens of genetically tested and viable embryos. The more you can choose between the closer you can get to your ideal combination of genes that you'll want to pass along to offspring.
To make selection of offspring by genetic testing viable we still need a few more pieces of biotechnology. First off, we need lots of information about what all the genetic variations mean. That information is now coming in a rapidly increasing torrent. Five years from now we are going to know about hundreds or thousands of genetic variations that contribute to health, size, musculature, coordination, personality, intelligence, endurance, and other characteristics. Second, we need the ability to test for thousands of genetic variations in a cell removed from an embryo. Well, the cost of testing for those genetic variations in cells removed from embryos will continue to fall rapidly. So that's not going to be an obstacle for much longer.
Our third and hard problem: The limited number of good ova. You can't test what you don't have. You can only choose among the viable fertilized embryos that can survive and develop into a baby. To solve this problem we probably need the ability to turn adult cells into eggs. Just turning adult cells into eggs isn't enough. The eggs also need all the regulatory state (called epigenetic state). They need the right genes activated and deactivated.
How long will it take to solve the problem of how to mass produce human eggs with correct epigenetic state from adult cells? Once that problem gets solved the rate of human evolution will accelerate by orders of magnitude.
In April last year, Prof Karim Nayernia, Professor of Stem Cell Biology at Newcastle University, made headlines by taking stem cells from adult men and making them develop into primitive sperm.
He has now managed to repeat the feat of creating the primitive sperm cells with female embryonic stem cells in unpublished work.
The next step is to make these primitive sperm undergo meiosis, so they have the right amount of genetic material for fertilisation.
But this is just another way to randomly choose chromosomes from two people to start a pregnancy. There's not much control over which genes end up in the new human. The really interesting step will come when individual chromosomes from different cells will become selectable to put together all the chromosomes used to start a pregnancy. With that capability will come a huge acceleration in the rate of human evolution.
Here's a technological step that will eventually make offspring genetic engineering easier to do. Though that's not why the technology was developed. In Vitro Maturation (IVM), which involves extracting eggs from an ovary at an earlier stage than In Vitro Fertilization (IVF), has been performed at a British hospital with successful births.
The first British babies - boy and girl twins - to be conceived using a new fertility technique have been born at the John Radcliffe hospital, Oxford.
In IVM, eggs are collected from the ovaries while they are still immature. They are then matured in a laboratory for up to 48 hours before being injected with a single sperm - a process called intracytoplasmic sperm injection (ICSI). A few days after fertilisation, the embryos are implanted into the mother's womb. Because fewer drugs are used, the cost of each IVM cycle is lower - at £1,700 - than standard IVF which can reach £4,300 per attempt.
IVM also really involves fertilization in vitro (i.e. outside of the body). So it is a form of IVF but called IVM.
IVM is important because it lower costs, reduces pain, reduces time, and lowers risk. Plus, it might work in cases where standard IVF fails. The advances in IVM development fit into a larger trend of improvements in so-called assisted reproduction technologies (ART). The techniques for cost and risk reductions are going to be ready and available when declining costs of gene testing technologies make artificial means of starting pregnancies far more desirable.
In standard IVF, the woman takes fertility drugs for five weeks to stimulate production of her eggs, which are then collected direct from her ovaries under the guidance of ultrasound, before being fertilised in the laboratory. The drugs cost between £600 and £1,500, with charges often higher in London.
The procedure is time consuming and uncomfortable and for the third of women with polycystic ovaries there is a one in 10 risk of severe ovarian hyperstimulation syndrome, a dangerous side-effect that in rare cases can prove fatal.
Since IVM will reduce risks and costs more women will opt for medical assistance to start pregnancies. The lowered risks will also play a big role in enabling much more widespread use of in vitro techniques once genetic testing advances to the point that women and couples gain the ability to select desired genetic traits. We need cheap DNA testing first to use to discover what all the genetic variations mean. Then with that knowledge prospective parents will use genetic testing to select embryos for implantation. Then selective pressures on human evolution will skyrocket. I figure given the continued rapid decline in the cost of DNA testing technologies we are somewhere between 5 and 15 years away from that turning point.
The first stage of the technique involves removing slivers of ovarian tissue through keyhole surgery.
Although these would be just millimetres wide, each sample would contain thousands of immature eggs.
The ovarian tissue is then frozen until the woman is ready to try for a baby. At that time, it will be stimulated with hormone chemicals to grow the immature eggs into mature ones ready for IVF treatment.
Mind you, the fertility researchers working on this problem think they are still 5 years away from offering this as a service. But I wonder: Are they trying to solve problems associated with initial extraction and freezing? Or are they working on how to solve the later stage of how to thaw out and grow eggs to maturity? If the latter then a woman who gets some ovarian tissue frozen today can probably count on the technology 5 to 10 years hence to thaw out and create eggs from that frozen tissue. If your biological clock is ticking then taking the first step might already make sense.
Dr Alan Thornhill, scientific director of the Bridge Fertility Centre, said: "It would mean we have got a pool of thousands of eggs at very little risk to the woman and relatively low cost because you avoid the huge drug costs. Instead of having up to 10 eggs to work with, with this you can have lots of eggs without the risk of over-stimulation.
Some day women in their 20s might routinely get their ovary tissue frozen in order to guarantee future availability of youthful eggs which have few genetic mutations. This will certainly enable many women to make babies in middle age. But it doesn't solve all the problems created by aging reproductive systems and aging bodies. The uterus ages as does the rest of the body and that aging reduces the ability of women to bring babies to term and increases the risk of defects.
The researchers working on this problem at the British clinics Bridge Fertility Centre and Care Fertility clinic are chasing a big market of affluent professional thirty something women who hear their clocks ticking. These women either haven't yet found Mr. Right (he's probably unlisted in the phone book or living under an assumed name) or the women first want to arrive at a place in their careers where they feel financially secure enough to make babies.
In the medium term biotechnologies will be developed that can turn normal cells from anywhere in the body into eggs. Also, as part of the general drive to grow replacement organs techniques will be developed to grow replacement ovaries and even replacements for other reproductive organs. Going out 30 to 40 years full body rejuvenation will totally eliminate age-related limits on reproduction. Then population growth will then become a huge problem. That will necessitate government-mandated limits on reproduction.
Cryos International, based in the Financial District, has gone to seed because the Food and Drug Administration banned sperm samples from 30 countries to prevent the spread of Creutzfeldt-Jakob disease, a rare, fatal disorder caused by eating beef contaminated with mad-cow disease.
Two years after the measure, Cryos has run out of offerings from such prized blond Norsemen as "Oluf," "Dagh," "Finn," "Ingi," "Jorn" and "Ante."
Speaking as someone who really appreciates blue and green eyed women I protest yet another example of overregulation by the US Food and Drug Administration. The Nordic blond hair and blue eyes are in short enough supply as it is. Why make the problem worse?
Sperm banks should consider opening up offices out in the upper plains states to recruit Nordic men. Some genetic testing could even provide genetic measures of just how Nordic is each donor.
New noninvasive techniques to select embryos for in vitro fertilization (IVF) could boost pregnancy rates and lower the number of risky multiple births. Scientists are using proteomics and metabolomics to screen the liquid that embryos are grown in prior to implantation in order to search for telltale signs of a healthy--or unhealthy--embryo. Some screening tools could be commercially available within the next year.
At some point in the next 10 to 20 years we are going to turn a corner where the advantages of IVF for starting a pregnancy will outweigh the advantages of natural sexual intercourse as a way to start a pregnancy. Improved methods for screening lots of embryos for healthiness might prove sufficient to make that happen. Embryos selected with proteonomics and genetic testing for defects might result in lower defect rates than come from making babies the old fashioned way.
A number of groups are chasing the development of better methods to identify good embryos.
Scientists at Molecular Biometrics, a biotech startup in Chester, NJ, are taking a different approach. They use near-infrared spectroscopy to detect specific molecules involved in oxidative stress, which can be an indicator of health in some tissues. Rather than look at single markers, the researchers have developed a specialized algorithm that can detect differences in the molecular profiles of viable and nonviable embryos.
They are doing a clinical trial with 1,500 patients to look for patterns.
Even if refinements in embryo screening for defects does not by itself make IVF more compelling eventually more sophisticated genetic screening will provide so many advantages that IVF will definitely become the preferred method for starting pregnancies. Reaching that point will happen once we learn the effects of most genetic variations and genetic testing becomes cheap. Then starting a pregnancy via IVF will allow women to select between dozens of embryos to choose the embryo that has the combination of chromosomes most likely to provide desired traits.
Some countries will restrict the use of genetic testing of IVF embryos to only allow selection against genetic defects. Those countries will find their future generations falling behind in international economic competition as parents in less regulated countries choose genetic variations that boost the intelligence of their offspring. Genetic testing policy will therefore become industrial policy and national security policy.
Most parents will select for higher intelligence and physical attractiveness of their children (I'm expecting a lot more blond hair and blue eyed daughters). They will also seek to avoid genetic variations that increase the odds of diseases. But beyond that what other preferences will they exercise when choosing between embryos? How outgoing or shy? How empathetic? How analytical or artistic? How altruistic or selfish?
If robots or artificial intelligences on the web do not take over the world then IVF genetic screening choices made by prospective parents and governments will do more to determine the kind of world we live in in the future than any other area of human choice.
Nice, France: Children born after embryo biopsy for preimplantation genetic diagnosis (PGD) do not show any more major malformations than those born after artificial reproduction technologies (ART) without PGD, a scientist will tell the annual conference of the European Society of Human Genetics today. Professor Ingeborg Liebaers, from the Research Centre for Reproductive Genetics, Free University of Brussels, Brussels, Belgium, will say that the results of her study of 583 children born after PGD was reassuring.
PGD is a new option for couples at risk of transmitting genetic diseases. Instead of carrying out a prenatal diagnosis followed by a termination of pregnancy, in vitro fertilisation (IVF) with intracytoplasmic sperm injection (where a sperm is injected directly into an egg) is performed, followed by genetic testing of the embryos. Only unaffected embryos are subsequently transferred to the womb.
“Because embryos are biopsied in PGD procedures, and this constitutes an additional manipulation of a delicate organism, we set out to study whether this had any effect on the health of children who were born as a result of this procedure”, says Professor Liebaers. The scientists first collected data on the pregnancies by giving questionnaires to patients on the day of the embryo transfer. Additional questionnaires were sent during pregnancy, at delivery, and later on to the patients, their gynaecologists, and paediatricians. Children were examined at 2 months and 2 years old.
A low risk from PGD will make IVF much more attractive once genetic testing becomes cheap. Genetic researchers will discover the effects of hundreds of thousands of mutations and they will make these discoveries at an increasingly rapid rate as a result of falling costs for genetic testing. Those discoveries will allow prospective parents to compare the genetic profiles of multiple IVF embryos to select the one that delivers the most preferred combination of genes.
If other studies verify the low risk of PGD found in this study then once genetic testing becomes cheap that low risk will help make embryo selection with PGD the preferred way to start pregnancies. That, in turn, will cause a huge speed-up in the rate of human evolution.
By maturing eggs with miniscule doses of fertility drugs after the eggs are removed with needles from ovaries fertility researchers have found a way to give women far smaller doses of fertility drugs for in vitro fertilization.
Clinical trials in Denmark have shown that a pioneering technique known as in-vitro maturation (IVM) has a success rate of 30 per cent, comparable to standard IVF procedures. The patient, however, does not have to take expensive fertility drugs that can carry serious side-effects.
This lowers costs, perhaps by as much as half. It also reduces the risks of side effects from fertility drugs. So IVF becomes less risky and less costly at the same time.
Professor Lindenberg, who works at the Nordica Fertility Centre in Copenhagen, explained: “We give a very low dose of a stimulating drug for three days early in the cycle and rescue up to ten eggs. For the first 24 hours a tiny amount of stimulating hormone is added to the culture, in fact one hundreth of the dose the woman would receive, and after that the eggs go on to mature in the culture alone.”
This is great news for those with fertility problems trying to make babies now. But in the longer run this advance will get even more widely used by those who start using pre-implantation genetic diagnosis to select embryos for implantation based on desired genetic characteristics.
Professor Bert Fauser - who carried out the study - said: 'Women are paying a high price financially and they are risking their health and psychological well being when low doses therapy will work for the majority of patients.'
A second study by Professor Fauser's team at the University of Utrecht found that high stimulation of the ovaries with hormone drugs created more chromosomally damaged embryos compared to women on mild stimulation treatment.
Milder methods to extract eggs will also reduce the risk for egg donors and therefore should lead to an increase the availability of donor eggs.
In the longer run I expect stem cell research to discover methods to create eggs from adult stem cells. This will solve the problem faced by women whose ovaries have gotten too old or never worked well in the first place.
At the conference where these results were presented the general theme was to find ways to reduce the severity of treatments used to boost fertility.
Dr Geeta Nargund, the organiser of the Congress on Natural Cycle and Minimal Stimulation IVF, and head of reproductive medicine at St George’s Hospital, London, believes it is time to stop giving women hormones to make them more fertile. In the week that IVF laws had a government shake-up, she says there is a back-to-basics approach to help women conceive that is safer, cheaper and, according to new studies presented by her peers at the congress, just as effective. Dr Nargund has pioneered techniques of scanning the ovaries for blood flow, which enables specialists to accurately predict which eggs are most likely to be fertilised successfully, doing away with the need to artifically stimulate the production of lots of eggs.
A new gene chip that can test 650,000 single letter genetic differences at once means we are getting close to finding large numbers of useful genetic variations. What causes IQ differences? We're going to know. We are finding out what causes hair color, skin color, and eye color differences. We are going to find out what causes differences in height, musculature, fat distribution (including breast size of course), teeth color, teeth enamel quality, facial shape, ear shape, and everything else that makes us look or think or feel differently from each other.
We are at the tip of a flood of information about human genetic differences. Prospective parents are going to use that information to choose embryos to get the kinds of kids they want. Look at brothers and look at sisters. Two brothers from the same parent can be greatly different in height, eye color, hair color, physical attractiveness, smarts, aggressiveness, and many other qualities. Couples are going to have the information they need to select among which of their own genetic variations they will pass down to their future children and I predict a substantial fraction of prospective parents will jump at the chance to make smarter and better looking children who are less prone to crime, depression, and assorted other problems.
The ability to fertilize several embryos, do genetic testing on embryos, and then choose the genetically most preferred embryo will accelerate the rate of human evolution. While many of the effects, such as intelligence boosting, will be beneficial I worry that different groups will go for different ideals and basically cause the human race to go off in divergent directions. I'm especially worried about divergences in that cause different tendencies in beliefs and moral sensibilities.
Will some choose genes that make their offspring more likely to be religious while others choose genes that make their offspring more likely to be skeptical? Will some choose genes which make people more likely to feel morally outraged while others choose genes that make their kids more amoral? Seems to me such choices will become possible and the human race could split into groups that cognitively see the world so differently that wars between them become inevitable.
In a forthcoming meeting of the Society of Natural Cycle Assisted Reproduction (ISNAR) Professor Bob Edwards (who initiated the first in vitro fertilization (IVF) pregnancy of the famous baby Louise Brown in 1978) and other fertility experts are expected to call for a reduction in the use of hormones that stimulate ovaries to produce eggs.
A conference of fertility experts this month will call on the IVF industry to rethink its approach. They say hormones used to "kickstart" the ovaries could cause chromosomal damage to more than half of eggs, rendering them useless. The treatments may also affect the womb lining, preventing embryos from implanting.
These fertility experts think that for some women the net effect of using the ovulation stimulation drugs might be a net harm for their prospects of getting pregnant.
While fertility drugs like Clomid (which causes a false signal of low estrogen to cause gonadotropin hormone release) are used for many IVF procedures they are not always necessary. Professor Edwards used eggs naturally produced by the menstrual cycle to start the pregnancy that produced Louise Brown. Also, it is possible to use lower doses of fertility drugs and some of these experts think fertility doctors should lower their doses.
The case against the fertility drugs has not been proven. But these fertility researchers and practitioners think the case is strong enough to argue for changes in procedures used by fertility clinics.
Another fertility pioneer, Robert Winston, the peer, said: "The trend is to get as many eggs as possible, but that may be counterproductive. From the research we've done, the main risk is that doing this produces chromosomal damage in at least half, if not 70 per cent, of eggs. New studies are needed to prove the drugs are causing the damage, but it is my strong suspicion that this is the case."
What is needed is another way to produce eggs for women with aged ovaries. That is coming. Within 10 to 20 years time advances in technologies for stem cell manipulations will produce eggs suitable for fertilization with sperm. It will become possible to take adult cells and expose the cells to a series of chemicals and/or gene therapies to turn them into embyronic cells and then stimulate them to divide into eggs.
Cutting back on fertility drug usage might not reduce success rates. In fact, a couple of recent findings both point the way to much higher rates of success for IVF attempts. See my posts Biopsy Doubles Success Rate For IVF Babies and Embryo Tests More Than Double IVF Pregnancy Rate.
Sheffield University professor Bill Ledger claims he has developed a test which will predict the decline of a woman's fertility by comparing hormone levels to results from other women.
The first two are Inhibin B and AMH, which decline as the menopause approaches.
The third is a pituitary hormone known as FSH - this tends to increase when the menopause nears.
A combination of the three will indicate the woman's reserve fertility, scientists say.
This is then plotted onto a graph showing the woman's position compared with the average fertility for women of the same age.
The predictive nature of this test means that the woman's ovarian reserve can be predicted for the next two years, says manufacturer Lifestyle Choices which is linked to the University of Sheffield.
The test costs £179 in British pounds or about $339 US.
Used in advance of IVF, it would give women judged to have a low chance of success time to prepare emotionally for the heartache of failing to conceive.
It could also allow those judged to be the least fertile to decide against having IVF, which costs up to £7,000 a time.
Prof Ledger said: "I don't think you can persuade a woman not to have a go with IVF because they are really desperate and it is a life-changing thing to decide you'll never have children.
"But you can soften the blow if you warn them from the start that the hormone results are dreadful and the chance of getting eggs, let alone embryos and babies is less than say, five per cent."
Women with poor odds can then consider donor eggs or adoption. Egg donation is harder to arrange in jurisdictions where donors can not sell their eggs. But British women who want to buy eggs could probably buy eggs in America. That'd increase the cost due to travel expenses. But some women can afford it.
Figures from the Human Fertilisation and Embryology Authority show that fertility rates plummet beyond the age of 35, reaching almost zero by 45. Miscarriage also becomes a risk the older women conceive. At 40, the risk is double that at 20 years, with 40% of all pregnancies leading to miscarriages.
Fewer eggs and less chance of a pregnancy going to completion both work against successful pregnancies once a woman reaches her 40s. Though some women age more slowly and still can have successful pregnancies into their 40s.
For those using in vitro fertilization (IVF or test tube babies) to start pregnancies the UK National Health Service will now offer to test for genetic diseases (pre-implantation genetic diagnosis or PGD) for 200 genetic diseases when the parents are known carriers.
Controversy has erupted over a new technique offered on the NHS which screens embryos for over 200 inherited diseases.
Doctors are heralding the test as 'revolutionary' for the diagnosis of genetic disorders.
But critics warn the ground-breaking technique is another step towards the creation of the 'designer baby'.
They fear extended genetic screening may eventually be used to create babies chosen for physical characteristics, such as blue eyes or blond hair.
What are fears for critics are thrills for many others. Word to the critics: If you manage to prevent the use of IVF and PGD in your own country then your country will slip down the ranks of the average national IQ league table as parents in other countries choose their embryos partially based on the expected intelligence of offspring. Your offspring will also become relatively less attractive than the new generations of countries that allow extensive use of genetic testing to choose embryos. Want to keep up with the Jones and the Kims and the Nguyens?
When genetic testing allows women to look at their own genes many will find they have too many genetic variations which they do not want to pass on to offspring. Some of those women will decide to find another female with more suitable genetic endowment who can be convinced to donate eggs. This will become more common in jurisdictions that allow payment for egg donation.
Computer automation and other advances allow testing for a large number of diseases.
The latest advances in automated computer analysis and genetic probes mean it is now possible to screen for virtually all currently identified genetic disorders. They include Fragile X Syndrome, Cystic Fibrosis, Diamond Blackfan, Krabbe's disease, Sickle Cell, Tay-Sachs disease and Marfan Syndrome.
Every year more genetic disorders will be identified. So far finding locations in genes that cause genetic disorders has been a big research focus. But we'll soon start seeing the discovery of genetic variations for hair color, eye color, various qualities of skin and teeth and nails, height, musculature, breast size, body shape, intelligence, personality tendencies, and other qualities. Once genetic tests for those features become available then I expect most upper class people to start using IVF plus PGD to start pregnancies.
They test the DNA of the prospective parents. If the prospective parents are carriers for potential genetic diseases then they test an embryo before implantation. The screening is expected to pay itself back many times over by avoiding the costs of taking care of many disabled children.
He said: ''I had a phone call from a primary care trust after a couple applied for funding, asking what it was all about. ''When I explained, the manager said, 'So this technique means we spend £20,000 and avoid the possibility of having to spend between £1 and £2 million caring for a disabled child. It's a no-brainer.''' Dr Fishel has to apply for permission from the fertility watchdog, the Human Fertilisation and Embryology Authority, in each couple's case to carry out genetic testing.
Think about where this leads to in the future. First off, genetic testing costs will fall so far that most people will get themselves genetically tested. So before even considering the idea of starting a pregnancy many people will know what harmful genetic variations they carry that they might want to avoid passing on to offspring. Since most couples will know about their harmful genetic variations those who have harmful variations will have more incentive to use in vitro fertilization (IVF) combined with genetic testing of embryos to choose which embryos to implant.
Economic class and intelligence levels will influence how this technology gets used. Since creation of each embryo costs money and since genetic testing also costs money those searching for ideal combinations of maternal and paternal genetic contributions will be limited by cost for how many embryos to create and test before choosing the best match. Those with more money will be able to test more embryos to get one that comes closer to their ideal.
I expect smarter people to place more importance on offspring intelligence than dumber people will. I also expect smarter people to be more willing to go the route of using IVF plus PGD to start pregnancies. So the extensive use of IVF and PGD will widen the existing gap between the smarter and dumber segments of societies.
The child could have been born in 1993 but its first experience of the world came 13 years later, or nine months after an embryo was pulled out of the freezer at a Spanish fertility clinic.
The clinic in Barcelona is claiming the world record for having brought about the birth of what could be termed the world's oldest baby. Conceived in a laboratory dish, but not used at the time, the embryo sat at minus 196C in a freezer cabinet awaiting its adoptive parents.
The original parents had donated the fertilised egg to the Instituto Marqués clinic after a sibling was born from a separate embryo successfully implanted in the mother's womb.
The ability to freeze embryos is useful for couples who have had to go the route of in vitro fertilization (IVF, a.k.a. test tube babies). They can store some embryos while trying to start a pregnancy with other embryos. If the pregnancy doesn't suceeed or if they decide they want still more children some embryos can be thawed out to try to start another pregnancy. One result of this practice is the gradual accumulation of thousands or perhaps tens of thousand of embryos in fertility clinics around the world.
Improvements in techniques to freeze embryos combined with the increasing use of IVF will increase the supply of surplus unused frozen embryos. Some Christian groups think those embryos are real human lives with souls and recruit married couples to try to start pregnancies with frozen embryos (a.k.a. embryo adoption) that are sitting in large numbers in freezers in fertility clinics. But advances in freezing technology and the increasing use of IVF both look set to increase the supply of embryos faster than Christians step forward to adopt them.
One trend I expect to emerge at some point: The ability to freeze embryos is going to become an added enticement for couples to start pregnancies with IVF rather than with good old fashioned sex. Why? Left-over embryos, freezable for decades, will serve as a sort of insurance policy should one or more of their kids die from an accident or disease. When the woman is still healthy enough to produce viable eggs couples could decide to do IVF, produce more embryos than they need, start one or more pregnancies, and then store some embryos in case the need arises or in case they just decide to have more kids when the woman reaches her late 30s or 40s.
Embryos are more robust than unfertilized eggs and embryos are easier to freeze and thaw. Alan B Copperman, MD. Director of Reproductive Endocrinology and Vice-Chairman of Obstetrics and Gynecology at the Mount Sinai Medical Center, says recent improvements in freezing and thawing techniques has increased success rates in use of frozen eggs.
In the fall of 2004, The American Society for Reproductive Medicine (ASRM) issued an opinion on oocyte cryopreservation concluding that the science was "promising" due to the fact that recent laboratory modifications have resulted in improved oocyte survival, fertilization, and pregnancy rates from frozen-thawed oocytes in IVF. The ASRM noted that from the limited research performed to date, there does not appear to be an increase in chromosomal abnormalities, birth defects, or developmental deficits in the children born from cryopreserved oocytes. The ASRM recommends that, pending further research, oocyte cryopreservation should be introduced into clinical practice only on an investigational basis and under the guidance of an Institutional Review Board (IRB). As with any new technology, safety and efficacy must be evaluated and demonstrated through future research.
The problems with egg freezing may eventually be solved by freezing earlier stage germinal vesicle eggs which, among other qualities, have membranes that are more permeable to cryopreservation compounds. But methods to extract eggs that are at that earlier stage might need refinement to get eggs that are relatively less developed.
Advances in egg freezing technology strike me as more interesting and with more implications than advances in embryo freezing technology. Egg freezing has two big potential purposes. First off, women who are looking for Mr. Right can freeze some eggs in case Mr. Right doesn't show up before their fertility declines. Second, egg freezing could become a way to increase the size of the market for donor eggs.
The same Alan B Copperman, MD quoted abave has done a recent survey of a small group of single women who had their eggs frozen. 80% said they would consider using donor sperm if they could never find Mr. Right.
Although the study was small — it involved 20 women — it suggests that the first group to take up the option of egg-freezing are doing so chiefly to take their fertility into their own hands.
“A number of women said they were interested in egg-freezing to take the pressure off the search for relationships,” the researchers said. “Cryo-preservation meant the freedom to wait, and to not settle for a mate because they were in a rush to conceive.”
Women with eggs sitting frozen in a freezer might well become more choosy about men as a result. Take away the sense of a biological ticking clock for reproduction and women may become more reluctant to compromise and less willing to lower their standards in order to find a guy to marry and make babies with.
Technological advances change the trade-offs people face. It changes trade-offs in relationships just much as it does in careers. Advances in assisted reproduction technology (ART) could change human relationships even more dramatically than has the birth control pill and other means of contraception.
In theory the ability to freeze eggs opens up the possibility of a much larger market for donor eggs with greater choices. Currently women looking for donor eggs can only choose among women who they can find to supply fresh eggs. But imagine the world 30 years from now. A woman could choose among eggs that come from eggs frozen over a period of decades and from donors who are no longer young and fertile. Egg donors could produce and store a large number of eggs when they are young and then gradually sell them over a period of decades.
But in many legal jurisidictions around the world a substantial legal obstacle exists for the creation of a donor egg market that spans across generations: Restrictions on the ability to pay for female egg donation services. Some jurisdictions ban the practice entirely. Currently the United States does not allow payment for eggs but only allows payment for the service of creating the eggs.
The United States is one of many countries in which legislation and social norms proscribe the selling of body parts. It is also the world capital of the genetic material market: No other nation trades in DNA so widely and freely. Hopeful mothers and cash-strapped college students have been trading cash for eggs for 20 years, calling the ova a “donation” and the money compensation for time and discomfort, thus avoiding the ban on sales.
How can a woman sell her eggs over a period of decades and claim her sales pay for discomfort she experienced 20 or 30 years ago? Would this claim stand up in court? I have no legal expertise. On the answer to that question hinges the future of a potentially much larger market for donor eggs.
When DNA testing becomes cheap and highly informative (on the outside within 10 years) the value of a small portion of all donor eggs will go up dramatically. Women who can show by genetic testing that they have the genetic sequences that are most in demand (high IQ, desired personality characteristics, good looks, desired hair and eye color, resistance to assorted diseases, etc) will find their eggs suddenly fetch even larger premiums than the current high prices for Ivy League egg donors who want to sell their eggs.
Do you want to sell your eggs? Women who think they might have the right genetic stuff could freeze their eggs now and then offer them for sale 10 or 20 years from now when they can prove with genetic tests that they have the genetic variations that the market most demands. Such women could freeze their eggs now and then if they meet Mr. Right when they turn 40 they can use a few of their eggs then to start a family. Whether or not they meet Mr. Right they can use other eggs from their frozen stash to sell once the market places a high value on their genetic inheritance.
Here's a technological advance sure to appeal to women in their 30s and 40s trying to get pregnant from their own eggs or from donor eggs. A new method of testing the viability of embryos produced via in vitro fertilization (IVF) more than doubles the success rate for attempts to start pregnancies.
Currently, only around 34 per cent of IVF cycles in the US result in pregnancy. By selecting embryos on the basis of their metabolic profile, Seli's team increased the pregnancy rate to more than 80 per cent in a pilot study, presented at the annual meeting of the American Society for Reproductive Medicine in New Orleans, Louisiana, last week.
Molecular Biometrics, a privately held metabolomics company, presented results of two clinical studies investigating the use of metabolomic profiling to assess embryo viability, a key step in the treatment of infertility by in vitro fertilization (IVF), at the American Society of Reproductive Medicine's 62nd Annual Meeting in New Orleans, LA.
In a podium presentation (O-270) titled Non-Invasive Metabolomic Profiling of Human Embryo Culture Media Correlates with Pregnancy Outcome, Principle investigator Emre Seli M.D., Ph.D. (et. al.) of the Metabolomic Study Group in ART at Yale University School of Medicine reported results of a retrospective multi-center study. The study was designed to assess embryo viability using a novel technology developed by Molecular Biometrics based on the metabolomic profiling of Oxidative Stress (OS) biomarkers. The goal of the technology is to identify metabolomic differences in viable verses non-viable embryos so only the highest quality embryos can be selected for transfer in IVF. This non-invasive test analyzes OS biomarkers in normally discarded culture media. The biomarkers are quantified using Molecular Biometrics' proprietary spectroscopic analysis and advanced bioinformatics.
The study group concluded that detectable differences exist in the metabolomic profiles found in culture media obtained from embryos that cause pregnancy compared to those that do not. The reported metabolomic parameters were established using two different forms of spectroscopic analysis, Raman and Near Infrared (NIR) spectroscopy, with media samples obtained from three different IVF programs. The metabolomic method achieved high sensitivity and specificity of > 85%.
What I'd like to know: Did some of the women produce only embryos that were unhealthy as measured by these methods? If you want to sell your eggs the ability to show a high rate of viable embryos in one egg sale would let you demand a higher price with later customers. This could be a boon to the egg donation market.
Each of the two spectroscopy methods was highly accurate by itself.
In the study, embryo culture medium from 163 embryos from assisted reproductive technology (ART) cycles using fresh donor and nondonor oocytes were evaluated. Normally discarded media from individually cultured embryos was collected at the time of embryo transfer on day 3, and analyzed using both Raman, and Near Infrared Spectroscopy. Metabolomic profiles of OS biomarker concentrations showed distinct differences between culture media of embryos that resulted in pregnancy compared to those that did not. Using a genetic algorithm with Raman analysis, novel OS molecular species were identified and statistically correlated with pregnancy outcome. The compiled outcomes resulted in a specificity of 82% and sensitivity of 95%. Likewise, analysis by NIR resulted in a specificity of 83% and sensitivity of 73%.
Expect a bigger market for assisted reproductive technology (ART) as a result of this advance. Initially it will decrease the demand for donor eggs by increasing the success rate of women trying to get pregnant from their own eggs. However, in the longer run this advance should increase the market demand for both assisted reproductive technology (ART) in general and donor eggs in particular. Why? Because it lowers the total cost of IVF. Success will happen in fewer attempts. Each attempt costs additional money, emotional pain, physical stress, and also costs time that ages a woman's body and makes her less capable of starting and maintaining a pregnancy.
Lower costs, higher assurances of success, and quicker results will entice more women to use IVF with their own eggs and, for some women, with donor eggs. Also, some egg donors will even be able to more quickly build up track records for producing eggs which result in higher percentages of viable embryos and successful pregnancies.
This result may not just increase IVF pregnancy success rates. It might even reduce the problem of birth defects. Some of the embryos that show up as problematic in these tests might be able to start pregnancies but eventually result in problems after birth. The ability to screen out marginal embryos might therefore reduce the incidence of birth defects. Biotechnological advances seem set to make reproduction with IVF preferred over natural sexual reproduction.
Could IVF-PGD one day become the preferred method of conception?
"It is technically possible," says Simon Fishel, a member of the team responsible for the birth of the first IVF baby in 1978, who now runs the Care Fertility group of clinics in the UK. There are, of course, huge obstacles, not least of which is the cost. "You have to pay per cycle," points out Fishel. "You can attempt to conceive naturally over 12 cycles in a year and it costs you nothing."
The "PGD" mentioned above, Pre-implantation Genetic Diagnosis, is the key to why IVF will probably become the preferred way to start pregnancies. Once genetic testing becomes cheap and the meaning of many human genetic variations becomes known IVF with PGD will provide prospective parents with a way to choose genetic variations for their children. That'll provide a way to avoid many genetic defects and to get children who are better looking, smarter, and with more other desired qualities.
Tests that can sort out high quality embryos will lead to the ability to implant only one embryo to start a pregnancy.
Even singleton IVF babies are around twice as likely to be premature or low birthweight. Again, however, multiple embryos could be to blame, because many IVF pregnancies start out as twin pregnancies. When single embryos are transferred, the differences in health vanish (New Scientist, 25 June 2005, p 14). Many countries limit the number of embryos that can be implanted and single embryo transfer could eventually become the norm.
This latest result reduces the costs of assisted reproduction technologies by reducing the number of cycles needed. It also will probably reduce premature births and birth defects. Once coming technologies make it possible to combine that with sophisticated and cheap genetic testing I predict most prospective parents will choose IVF over natural sexual reproduction.
Sometimes scientists discover amazingly useful things by accident. Nava Dekel, a professor at the Weizmann Institute in Rehovot Israel, was part of a team examining a protein's role in allowing a fertilized egg to implant in a woman's uterus. The team did biopsies on a dozen women who were having problems starting pregnancies and 11 of the 12 became pregnant. The team suspected that biopsy increases fertility and so did a study of biopsy's effect on larger number of women. They discovered that biopsy (presumably of the uterus) doubles the success rate of implanting embryos created by in vitro fertilization (IVF).
"We decided to conduct a larger study of this phenomenon, and enlarged the group to 140 women. We explained the goals of the study, and 50 of them volunteered to have the biopsies. The rest were used as a control group," she said.
The results showed that the women who underwent the biopsies had a success rate of pregnancy double than the women who underwent the standard IVF treatment without biopsy. In other words, having a biopsy doubled a woman's chances of becoming pregnant.
Three Israeli institutions now use biopsy as a standard way to increase fertility and Professor Dekel expects American fertility clinics to soon copy this practice. This one practice could cause a large increase in the number of babies created by IVF. If the technique boosts the success rate it will also greatly reduce the cost of IVF because it will reduce the number of repeat attempts necessary to start a pregnancy.
Another Israeli study mentioned in the same article found that immune cells play a key role in releasing a compound that causes placental growth. So one cause of infertility might be immune system malfunction.
Methods to increase the reliability of IVF will increase IVF's use both with a female's own eggs and also with egg donation. So I expect this advance will increase the demand for donor eggs. In legal jurisdictions where compensation of egg donors is legal this advance might raise the prices for donor eggs.
IVF is going to become cheaper and more reliable. At the same time, an accelerating rate of discovery of the significance of genetic variations will produce a wealth of knowledge of genetic variations to test for before implantation. This will result in the greater use of Pre-implantation Genetic Diagnosis (PGD or PIGD) used in conjunction with IVF to choose embryos to implant. Cheap IVF and cheap and powerful PGD will increase the attractiveness of IVF as the method to use to start pregnancies. That will lead to an acceleration in the artificial (i.e. by conscious human choice) selection of genes as opposed to natural selection. What would Charles Darwin make of this development?
Does in vitro fertilization (IVF ) work better using fresh human eggs as compared to eggs that were frozen and then thawed? Kutluk Oktay MD and colleagues at the Cornell's Center for Reproductive Medicine and Infertility New York City looked at the relative success rates of using freshly donated human eggs versus thawed eggs to start pregnancies that go to term and produce live births. They compared two methods of freezing called slow-freezing (SF) and vitrification (VF) as well as freshly harvested eggs. IVF was done with intracytoplasmic sperm injection (ICSI). Fresh eggs produced almost 3 times the number of live births as eggs using the best freezing method, slow freezing. (ET stands for Embryo Transfer)
Live-birth rates per oocyte thawed were 1.9% and 2.0% for SF and VF, respectively, before June 2005. Live-birth rates per injected oocyte and ET, respectively, were 3.4% and 21.6% for SFM and were 6.6% and 60.4% for IVF with unfrozen oocytes.
Yet the 21.6% success for the better freezing method is high enough to be usable. That's good news because frozen eggs have a few benefits. First, women who are going to undergo medical treatments (e.g. chemotherapy for cancer) might become sterile or suffer sufficient damage to their ovaries that their eggs would be at risk of producing defective babies. Extracting and freezing eggs from a woman before she undergoes a medical treatment opens up the possibility of still being able to have healthy children afterward if the illness can be cured.
Another reason to freeze eggs is to allow a young woman to store some eggs away to use to have children in her late 30s or 40s when fertility declines drastically.
A third possible reason to freeze eggs is that it opens up the possibility of a much larger market of donor eggs. A woman could have eggs harvested and stored for transport to wherever a market demand for her particular eggs exists. Then buyers could have much larger selections to choose from. Egg donation will become more commonplace if women can have eggs harvested while she is young to be sold for decades afterward.
Many countries do not allow the sale of donor eggs. However, in the massive market called the United States of America egg selling is allowed. One center in Texas even will put together donor eggs and sperm and ship already fertilized embryos to IVF clinics for implantation.
The Abraham Center of Life allows people to order custom-made embryos and have them shipped to an IVF clinic for implantation.
The embryos are created with the eggs and sperm of rigorously screened, "qualified" donors who have never met each other. Conception occurs as the embryo bank fills its orders. Customers can even specify the eye and hair colour that they would like their baby to have.
They can't guarantee the hair and eye color just yet. But with advances in genetic testing fertility clinics will eventually be able to offer high probabilities for sex, appearances, intelligence level (high IQ will become very popular), personality type, disease risks, and other characteristics.
Advances in egg freezing and thawing methods combined with advances in DNA testing and IVF will increase the advantages of using donor eggs and therefore increase the demand for egg donors. See my posts High Intelligence Sperm and Egg Donor Prices Rising, The Growing Market For Donor Eggs, and More Single Women Using Sperm Donors. I also predict the development of a larger market for donor eggs and sperm will make humans more genetically determined and less influenced by their environment. See my post Children Of The Future May Be More Genetically Determined.
NEW HYDE PARK, NY – An obstetrician well known for his care of and research into multiple-birth pregnancies has found that dietary changes can affect a woman's chances of having twins, and that her overall chance is determined by a combination of diet and heredity. By comparing the twinning rate of vegan women, who consume no animal products, with that of women who do eat animal products, Gary Steinman, MD, PhD, an attending physician at Long Island Jewish (LIJ) Medical Center in New Hyde Park, NY, found that the women who consume animal products, specifically dairy, are five times more likely to have twins. The study is published in the May 2006 issue of the Journal of Reproductive Medicine, available May 20.
The Lancet recently published an invited comment by Dr. Steinman on dietary influences on twinning in the journal's May 6 issue.
The culprit may be insulin-like growth factor (IGF), a protein that is released from the liver of animals -- including humans -- in response to growth hormone, circulates in the blood and makes its way into the animal's milk. IGF increases the sensitivity of the ovaries to follicle stimulating hormone, thereby increasing ovulation. Some studies also suggest that IGF may help embryos survive in the early stages of development. The concentration of IGF in the blood is about 13 percent lower in vegan women than in women who consume dairy.
The twinning rate in the United States has increased significantly since 1975, about the time assisted reproductive technologies (ART) were introduced. The intentional delay of childbearing has also contributed to the increase of multiple-birth pregnancies, since older women are more likely to have twins even without ART.
"The continuing increase in the twinning rate into the 1990's, however, may also be a consequence of the introduction of growth-hormone treatment of cows to enhance their milk and beef production," said Dr. Steinman.
So there are multiple factors increasing the incidence of twins: older age at time of reproduction, use of in vitro fertilization (IVF), consumption of dairy products, and possibly the use of growth hormone treatment of cows.
The increased incidence of twins has one big drawback. If you want to have smart children then avoid twins.
OBJECTIVES: To determine whether twins have lower IQ scores in childhood than singletons in the same family and, if so, whether differences in fetal growth explain this deficit. DESIGN: Cohort study. SETTING: Scotland. PARTICIPANTS: 9832 singletons and 236 twins born in Aberdeen between 1950 and 1956. RESULTS: At age 7, the mean IQ score of twins was 5.3 points lower (95% confidence interval 1.5 to 9.1) and at age 9, 6.0 points lower (1.7 to 10.2) than that of singletons in the same family. Adjustment for sex, mother's age, and number of older siblings had little effect on these differences. Further adjustment for birth weight and gestational age attenuated the IQ difference between twins and singletons: the difference in mean IQ was 2.6 points (-1.5 to 6.7) at age 7 and 4.1 points (-0.5 to 8.8) at age 9. CONCLUSIONS: Twins have substantially lower IQ in childhood than singletons in the same family. This effect cannot be explained by confounding due to socioeconomic, maternal, or other family characteristics, or by recruitment bias. The reduced prenatal growth and shorter gestations of twins may explain an important part of their lower IQ in childhood.
I wonder if better nutrition for mothers pregnant with twins could at least partially compensate for the effects of carrying twins on brain growth. Maybe a diet higher in omega 3 fatty acids, choline, and/or other nutrients could compensate?
Update: Since twinning rates fall during periods of food shortage (as happened during World War II) another interpretation of these results is that vegan women have fewer twins because they are nutrient deficient.
Other scientists say vegan women may bear fewer twins because they are less well nourished. Dr Paul Haggarty of the Rowett Research Institute in Aberdeen says there may be other nutrients that vegan women lack.
So maybe dairy consumption isn't causing an unnatural outcome? Then again, maybe it is.
Research has shown for the first time that human eggs may develop directly from cultured ovarian surface epithelium (OSE) cells derived from adult human ovaries. Oocytes derived from the culture of OSE cells developed in vitro into mature eggs suitable for fertilization and development into an embryo. These findings, published today in the Open Access journal Reproductive Biology and Endocrinology, offer important new strategies for use in in vitro fertilization and stem cell research, and cast doubt on the established dogma on the fetal origin of eggs in adult human ovaries.
It is now well established that fetal mammalian eggs originate from somatic stem cells. More recent research of adult human ovaries has shown that oocytes and granulosa cells (the layer of small cells that form the wall of the ovarian follicle) may originate from OSE cells and assemble together to form new primary follicles – the structures that grow and rupture during ovulation to release mature eggs. However, definitive proof that new oocytes may develop in adult human females will be if they can be found to differentiate in vitro from OSE cells derived from adult human ovaries.
For the first time, Antonin Bukovsky and colleagues from the Department of Obstetrics and Gynecology of the University of Tennessee, United States, have shown that human eggs and granulosa cells) can develop from cultured OSE cells. By scraping cells from the surface of adult ovaries and growing them for 5 to 6 days in the presence of an estrogen-containing medium (phenol red) to stimulate their growth, the team was able to produce new human oocytes in vitro.
The oocytes cultured in this way are viable and went on to successfully complete the first meiotic division to become mature human eggs – capable of being fertilized and developing into an embryo. These in vitro findings support earlier in vivo studies by Bukovsky and colleagues that OSE cells are bipotent; capable of differentiating along two developmental pathways and becoming either egg or granulosa cells. The authors speculate that this bipotent differentiation may represent a sophisticated mechanism created during the evolution of female reproduction, and not seen in ovaries of female prosimians (ancestral primates) or mice carrying germline stem cells.
Women in their early or mid 20s who think they may have many years before they will have children could opt to have some OSE cells extracted from their ovaries to be used 10 or 20 years later to start pregnancies.
The ability to produce mature human eggs from adult ovaries in vitro has several potential applications in human reproduction. The technique of harvesting cells from the ovarian surface is relatively easy, can be accomplished by a laparoscopy technique, and yields more cells for use for in vitro fertilization. The ability to develop human eggs from OSE cells may help women with reduced fertility and premature menopause, who lack follicles in their ovaries, to have a better chance of conceiving through in vitro fertilization. Eventually, frozen OSE cells from younger females may be preserved for later production of fresh eggs. This may prevent the occurrence of fetal genetic alterations, which are often associated with an advanced maternal age. In addition, a colonization of premenopausal ovaries with younger oocyte and granulosa stem cells may establish a new cohort of primary follicles. This may result in a 10- to 12-year delay of the onset of natural menopause. Also, these ovarian stem cells could be used to generate several cell types used in stem cell research, and fertilized eggs produced in this way could produce cells capable of giving rise to embryonic stem cells for use in research and therapeutic applications.
Women whose ovaries are no longer producing eggs might eventually be able to use this technique to have babies. Reproduction will be extended into a woman's late 30s and 40s. Professional women who now pursue career success and delay too long to have children might finally have a biotechnological solution to their predicament. My guess is this technique will be used most heavily by highly educated career women.
Note that this technique will probably be an attractive option for women in their 30s who are still fertile. Old eggs have greater risk of genetic defects. Use of OSE cells extracted and frozen at a younger age would probably lower the risk of genetic risks. Even OSE cells extracted from a women in her 30s when she wants to have a child might produce eggs which are at less risk of genetic defects.
Any woman who has older friends who are going through menopause may be attracted to the idea of delaying menopause. Why be woken up by severe painful hot flashes? Why start feeling like you are crazy or furious or depressed or lethargic? Why lose the ability to concentrate? Why suddenly feel frigid and disgusted at the sight of your husband? ( I'm relaying stories from fifty something women friend talking about themselves and their friends going through menopause) If you can delay all that stuff you might be able to delay it till better treatments for relieving menopausal symptoms become available. On the other hand, by delaying menopause you might also increase your risk for some of the female cancers.
Researchers working with human embryonic stem cells are forming collaborative relationships with doctors at fertility clinics because the two groups are pursuing answers to some of the same questions. The development of techniques to better grow stem cells in laboratories will lead to better techniques to grow an embryo before it is implanted in a would-be mother's womb. Researchers in the field expect embryonic stem cell research to produce knowledge helpful in improving assisted reproduction technologies before the same research leads to development of stem cell therapies and growth of replacement organs.
Stem cell laboratories often use many of the same methods as those used to help couples conceive.
"These are technical advances," Snyder said, citing examples such as finding the best ways of thawing and freezing embryos or determining which materials make the best surfaces on which to place reproductive materials in a laboratory.
Better knowledge about fetal cell feeding and chemical signalling holds the promise of identifying the reasons why miscarriages occur and the development of ways to prevent miscarriages.
Scientists are only beginning to glimpse all the intricate interactions that go on between the cells of the embryo and its environment. By using placental cells in the laboratory, Fisher said, researchers for the first time are able to "characterize the interactions" each step along the way.
Those findings may help shape stem cell treatments. Back in the IVF clinic, Cedars hopes to use the findings much sooner.
"You can take it one step further and apply it to the fetus in utero, into perhaps better ways to promote fetal health," she said, adding that some of the greatest frustrations in IVF occur when someone manages to become pregnant and then miscarries.
The researchers interviewed for the article say they think it ironic that while embryonic stem cell research is seen in some quarters as a product of killing of early stage human life the research will be used eventually to avoid miscarriages and to allow more pregnancies to be started.
Of course the opponents of embryonic stem cell research could argue that some of the information that will be discovered by human embryonic stem cell research could also be discovered by embryonic stem cell research on other species. Still, any new technique that appears to help to grow non-human embryonic cells still has to be verified as working on human embryonic cells as well. In fact, the various mammalian species differ significantly in the difficulty of doing reproductive cloning and in growing their embryonic cells in culture. So not all knowledge is going to be equally applicable across species.
Since the state of California is now going to fund human embryonic stem cell research at a high enough level to make substantial progress it seems reasonable to expect many advances in the coming years in techniques for assisted reproduction and for maintaining healthy pregnancies. The ethical arguments are going to continue. But the science is going to be done.
She underwent fertility treatment for nine years, including procedures to reverse the effects of menopause, before being artificially inseminated and then having a Caesarean at 33 weeks.
Most of the news reports on this story do not mention the most important point: she had a donor egg.
Adriana Iliescu, who was artificially inseminated using sperm and egg from anonymous donors, delivered her daughter Eliza Maria by Caesarean section, doctors at the Giulesti Maternity Hospital in Bucharest said. The child's twin sister was stillborn, they said.
So drugs could get her reproductive tract to the point where she could start and maintain a pregnancy for over 7 months.
Marinescu said Iliescu was successfully inseminated on the first attempt, and that she initially was carrying triplets but lost the third fetus after nine to 10 weeks.
The girl was born prematurely by Caesarean section after her twin sister died in the womb, the hospital said.
When it becomes possible to rejuvenate reproductive tracts the world could be faced with a population explosion. Career women especially can be expected to have children when they are finally able to do so with assurance in their 40s, 50s, and 60s. Here is the future for the most ambitious and talented women: Make it to the top of the corporate ladder, and stash away millions. Then get rejuvenation treatments to get young again, retire, and make babies.
Artificial wombs will also eventually remove the limits on reproduction caused by aging. Cloning techniques combined with rejuvenation techniques will even allow women to make babies with lab-produced eggs rather than with ovaries. Then there will be no need for women to burden themselves with menstrual cycles or pregnancy. My guess though is that some women will still opt for pregnancy for the experience.
Once rejuvenation becomes possible I predict that some or all governments will eventually limit the number of births each woman can have. Otherwise rejuvenated women who like children could have dozens or hundreds of children over a period of centuries.
Chicago, IL. November 8, 2004. Arryx, Inc. announced today that it has added an infrared (IR) product to its line of BioRyx(R) 200 optical trapping systems. The BioRyx(R) 200 IR system extends Arryx’ proprietary, three-dimensional holographic laser tweezer technology into the infrared portion of the spectrum. Arryx’ easy-to-use real-time trapping software allows users to create a variety of infrared traps and simultaneously monitor and record fluorescence from a broad range of dyes. This gives researchers in biology and nanotechnology the unique ability to manipulate hundreds of microscopic objects, from blood and cancer cells to DNA and nanotubes, independently and simultaneously in three dimensions.
One of the initial applications of their technology is going to be the sorting of bull sperm to select cow gender in order to reduce the number of less valuable male cows (only females can make milk).
Arryx’ next product is its cell-sorting equipment, the CelRyx(TM) system. The initial applications of CelRyx(TM) system are designed to increase productivity and profitability in the cattle and dairy industries, by sorting cattle sperm for viability and gender selection, and the blood-bank equipment industry, by processing blood components.
"We have a partnership with a company involved in artificial insemination for cattle. With this system [expected to be out in 2005], you put cattle semen in one end of the machine and sorted cells (come) out the other," he said.
A physicist who was at the University of Chicago made scientific advances that made the laser tweezer technology feasible.
But it took David Grier, then a University of Chicago physicist and now director of the Center for Soft Matter Research at New York University, to develop the method to control multiple items at one time with a single beam. His technique involves splitting laser beams into multiple "beamlets," which operate on the nano level to control as many objects as desired.
For information and background on the scientific and technical work that led to the implementation of laser tweezers, feel free to browse Dr. David G. Grier's Web site: http://physics.nyu.edu/grierlab/.
It is not clear whether Arryx's technology will ever be offered for sex selection of human offspring. Another company, Microsort, already offers human baby sex selection services using a different technology. Microsort's approach is not 100% accurate and requires in vitro fertilization (IVF). So it has some downsides. Note that Arryx is going to offer sex selection for cows. My guess is their approach is cheaper since it would have to be for animal husbandry. If Arryx's technology could sort a larger number of sperm then it opens up the potential for initiating pregnancies with artificial insemination without IVF and without the need to harvest eggs to use in IVF.
Eventually much easier and lower cost pre-conception sex selection technologies will be available for human use. As it stands now cheap ultrasound technology and selective abortion are already causing large excesses in male births in Taiwan, China, and India. Imagine what will happen worldwide as costs and risks of sex selection drop.
Arryx has also made a deal with a company called Haemonetics to developed their technology for blood processing. Their technology looks promising for all sorts of manipulations of large numbers of small things simultaneously.
Some British scientists have proposed the use of in vitro fertilization techniques that will create a child with 3 genetic parents where one of the parents donates only mitochondrial DNA (mtDNA).
The research application from Doug Turnbull and Mary Herbert at the University of Newcastle will be decided upon by the UK's regulatory body, the Human Fertilisation and Embryology Authority, over the next few weeks. The procedure would involve fertilising a woman's egg by in-vitro fertilisation outside the body and transplanting the fertilised nucleus to an egg from another woman which has had its nucleus removed.
The resulting baby would have mitochondrial DNA from the woman who donated the egg. The nuclear DNA would be an even split between the two original parents who provided and fertilized the first egg. Since the nucleus of humans has about 2.9 billion DNA letters and the mitochondrial DNA has only 16,569 DNA letters the amount of DNA contribution by the egg donor will be extremely small. Those 16,539 letters code for 13 genes that are involved in the mitochondrion's breaking down of sugar to produce the energy molecules NADH and ATP.
The chief value of this technique is that it would allow women who have diseases caused by harmful mitochondrial DNA mutations to have offspring that do not suffer from their mother's mutation. Also, there is evidence that mitochondrial DNA variations have an influence on life expectancy. So one can imagine future parents wanting to select mtDNA to give to one's child that would add a one or two decades to their life expectancy.>
In a broader context this is one step down a much longer road where children will be born who have many genetic parents. In the future with more advanced technqiues for manipulating cells (perhaps using microfluidics) the 23 pairs of individual nuclear chromosomes that make up a single cell's DNA complement could be taken from different people to combine in the nucleus of a single embryonic cell. That cell could then develop into a full adult. Once it becomes possible to extract and insert individual chromosomes the nuclear DNA for a single embryo could be built using chromosomes taken from 46 different people.
The ability to combine chromosomes from lots of different people is one of the ways that people will create kids who combine many different most desired features into individual people. This will have the effect of speeding up human evolution because as desired features are more rapidly selected for then of course less desired features will be just as rapidly selected against.
In Western societies I expect women will be doing most of the selecting of DNA donors. In some other societies men will be doing more of the selecting. Given the differences in male and female ideals and the differences in ideals between societies it seems reasonable to expect a greater divergence in the genetically determined and influenced characteristics in people in different parts of the world. Though perhaps in some qualities there will be a convergence as, for instance, blond hair and blue eyes are popular in so many places.
My guess is that higher IQ will be universally popular. But in other cognitive characteristics I expect to see divergences between populations. For example, not all populations will place equal value on introversion versus extroversion. Similarly, I expect to see differences between societies in choices for genetic variations that influence the tendency to be faithful in marriage. Some societies will want more masculine men or feminine women than other societies.
The use of Preimplantation genetic diagnosis (abbreviated PGD or PIGD) does not increase risk of birth defects.
The Reproductive Institute of Chicago study looked at 754 babies born after IVF pregnancies where preimplantation genetic diagnosis was used.
It found they were no more likely to suffer birth defects than babies born after natural pregnancies.
It is not clear that the BBC reporter got this story exactly correct. First of all, the risk of in vitro fertilization (IVF) pregnancy is hard to compare to natural pregnancy because people using IVF already have a problem getting a pregnancy started. IVF users tend to be older on average and to have problems starting and bringing a pregnancy to completion. I suspect that the original finding of the paper might support the idea that IVF with PIGD is no riskier than IVF alone. But I kinda doubt that they could prove that IVF is no riskier than normal pregnancy started with sexual intercourse.
The abstract does not provide enough details. Also, the Reproductive Institute referred to above is really the Reproductive Genetics Institute. They do not appear to have a press release on this paper on their site. (Though their site's layout could really stand for some improvement to make it easier to find stuff on it)
Once DNA testing becomes much cheaper and the significance of many more genetic variations becomes known expect to see embryo screening to become much more widely used. The advantage is that it allows people to control which genetic variations they pass along to their offspring. A person apprised of what is on each of their chromosomes is likely to decide for each pair of chromosomes that a particular one of each pair would make a much better choice to pass on to offspring. The decisions will be made for reasons of hair color, eye color, intelligence, personality, risk of skin disease, risk of depression, facial shape, height, tendency toward obesity, or countless other qualities.
One interesting aspect of this latest report may not be immediately apparent: On day 3 an embryo has 8 cells and one is removed to use to do the PIGD testing for genetic defects. Well, the embryo can continue to grow without problems even though one cell has been removed from it. Think about that 1 cell that has been removed. It could be stored. It could be grown up to produce a large number of cells to use in stem cell therapies. Currently there is a lot of opposition to the use of embryonic stem cells in large part because the creation of embryonic stem cell lines is seen as a procedure that destroyed a potential life. But if that single removed cell could be cultured and grown up to produce lots more additional cells then no potential life would need to be extinguished. Any IVF pregnancy could also produce useful stem cells.
Also see my previous post Fetuses Give Pregnant Women Stem Cell Therapy for another possible way around problem of the ethical opposition to embryonic stem cell therapy.
Experiments by Howard Hughes Medical Institute (HHMI) researchers have revealed it might be possible for randomness in gene expression to lead to differences in cells — or people, for that matter — that are genetically identical.
The researchers, HHMI investigator Erin K. O'Shea and colleague Jonathan M. Raser, both at the University of California, San Francisco, published their findings May 27, 2004, in Science Express, the online edition of the journal Science.
Raser and O'Shea used an indicator technique developed by Elowitz to detect noise in gene expression. They engineered yeast cells to produce blue and yellow fluorescent indicator proteins under the control of the same “promoter” — the segment of the gene regulating its expression. In this scheme, if there were no noise, every cell would appear the same mix of blue and yellow color under the microscope.
However, if any noise crept in, it would produce a variation in colors among the cells. This color variation could then be measured to determine the amount of noise that was present. This method eliminated any influence of external environmental factors or variables such as differences in cell type, since the two genes were operating inside the same cell.
After using this technique to study the function of various promoters, the scientists concluded that noise did, indeed, affect gene expression in the yeast cells. They also found that different promoters produced different amounts of noise.
This suggests why some twins are different in some ways. But note the point that not all promoters are shaped to produce the same amount of noise. This is important. Picture two hypothetical pairs of twins where one pair looks like it has identical height and another pair is an inch different in height. For a gene that controls height the first pair of twins who are more similar in height might have a promoter region which has lower noise than the matching promoter region in the second pair of twins. But since there are many variations in promoter regions for many genes that regulate different aspects of growth and development our hypothetical pair of twins that is more similar in height might be less similar in, say, personality than the seond pair due to having promoter regions for personality genes that are more noisy.
A lot of twins studies which have sought to discover how much of each characteristic is inherited have been confused by the effect of genetic regulatory noise. Some differences between twins are not a result of parents, schools, social environment, or nutrition because there is noise in the machine.
I predict that in the future parents who opt to genetically engineer their offspring will choose less noisy promoter regions for genes which control characteristics that the parents consider most important. Parents might be willing to gamble on some characteristics that they deem to be less important. But if a parent is told that left to chance there is, say, a 10% chance their offspring could be a psychopath or prone to excessive anxiety due to noisy gene promoter regions my guess is that many parents will opt for some genetic engineering on their future baby's fertilized egg in order to ensure the result will be within the range of possibilities that the parents consider acceptable.
My guess is that parents will rarely choose to introduce more noise and more unpredictability of outcomes for characteristics for which they hae no strong preferences. Either the parents will not intervene or their desire for certainty will motivate them to intervene to make outcomes more deterministic and predictable. Therefore I also predict that children of the future will, on average, have more characteristics that are strongly determined by their genes than is the case today.
Viagra seems to speed up the acrosome reaction, so that by the time the sperm reaches the egg it has no digestive enzymes left to penetrate the outer layer. Sperm that have undergone this process are known as fully "reacted".
The researchers tested 45 samples of semen. They found that up to 79% more sperm were fully "reacted" in samples treated with Viagra.
This fertility finding contrasts with human data from clinical trials: Viagra’s effect on sperm movement and function was extensively studied, says Larry Lipshultz of Baylor College of Medicine in Houston, Texas who has been involved in trials of Viagra and its competitors, Levitra and Cialis. "I've reviewed all the data and never seen a fertility problem," he says.
The team is now studying the effects of Viagra on the sperm of men actually taking the drug. The initial findings in 17 men show Viagra does speed up sperm.
It is interesting to note that some men whose sperm fail to fertilize in convention IVF may have insufficient acrosome activity. So the use of Viagra by men who are trying to use IVF to start a pregnancy may be making their existing cause of the need for IVF even worse.
Most sex is for reasons other than reproduction. But these results suggest that those intending to start a pregnancy and those who are not adequately protecting against the possibility of pregnancy ought to think twice about using Viagra. Certainly if you are going to try to do IVF think twice about using Viagra to help get the sperm sample.
This work obviously needs to be repeated for Levitra and Cialis as well.
John Gonzalez, creator of the existing website www.ManNotIncluded.com for trading human sperm, has now expanded into human donor egg trading with his new website www.WomanNotIncluded.com. His organization is London based and in Britain actual donors can not be paid for eggs.
The donor receives expenses, but in the UK they are not allowed to be paid directly for their eggs under the Human Fertilisation and Embryology Authority (HFEA) regulations.
The database is global, meaning a couple wishing to use a donor from another country could buy the eggs without the same limits on expense costs.
One consequence of this silly British government rule: Brits will buy more of their eggs abroad.
Joining Fee access to database search £145.00
Criteria based search of database by our staff producing results £ 537.00
Select a donor introduction £620.00
Donor selection payments must be made prior to details being passed onto clinic of your choice.
At the time of this writing the exchange rate is about $1.90 per pound. So US dollar pricing is not quite double the price in British pounds.
So far, 40 donors have signed up to the site from the UK and France. Donors must supply details about their health history, ethnic origin, hair and eye colour - and can also include information about their academic achievements.
In the United States, where paying women to be egg donors is legal, the price for what are judged to be higher quality eggs (e.g. from Stanford and Ivy League undergraduates) can range as high as $50,000. Check out the comments section of that post and you will see many woman posting comments offering to sell their eggs. Less highly sought donors may expect to be paid around $5000. Though there is not enough transparency in the market to be able to predict what any one woman might hope to get for selling her eggs.
My prediction for the future is that the fraction of pregnancies started with donor eggs and donor sperm will rise quite dramatically. The big incentive for using donors will come once persona DNA sequencing makes it possible to know exactly what genetic advantages one can gain by using particular donors. I predict that the use of donor sperm will become especially desirable for women because it is far easier to use donor sperm than donor eggs.
Though another option that may become popular (provided it is not outlawed by an international treaty) is what I call Cloning Plus. With Cloning Plus people will be reproduce themselves with clones which have many of their own genetic flaws removed. Imagine, for instance, the appeal to a woman to have a daughter who looks like her except for being a little bit prettier (straighten those teeth and make them perfectly white and well-shaped), resistant to allergies, resistant to acne, slightly more blond hair, smarter, less prone to depression, and generally better in every way some women wishes she was herself.
Need an embryo to start a pregnancy? If you are in New Zealand you may find yourself going through the same sorts of screening steps that baby adopters routinely do now in many jurisdictions.
Infertile couples adopting an embryo may have to undergo police checks to determine if they are suitable recipients. The move is being considered by the National Ethics Committee on Assisted Human Reproduction (NECAHR) as it sets guidelines for embryo donation for reproductive purposes.
Conceptually this is not all that different than screening people who want to make babies from their own sperm and eggs. So you have to use someone else's egg. Why is that any more reason to screen for parental competence and character than if one uses one's own egg?
Recipient screening is only one side of the issue. In Denmark a sperm bank is doing criminal background checks on sperm donors.
In Denmark, the world's biggest sperm bank - Cryos International Sperm Bank in Aarhus - has been forced to start screening donors for any criminal record after it emerged that a man who killed his two baby daughters was on its books.
Think about how this is going to develop once alleles are identified that contribute to criminality. There will be calls to prevent men with criminal tendencies from reproducing. But rather than an outright ban on reproduction of criminals there might be a move to prevent criminals from passing on just the genetic variations that make the biggest contribution to criminality. How could that be done? pre-implantation genetic screening. A recent advance in biotechnology may make pre-implantation for genetic variations easier to do.
Hundreds of cells have been grown from a single cell taken from an early mouse embryo. If the same feat can be repeated in humans, it would make screening embryos for genetic defects during IVF much easier and more accurate.
Pre-implantation genetic screening is already becoming popular for sexual selection. Surprisingly, in Australia genetic screening for sex selection is being done more often to select for a girl than to select for a boy.
But at Sydney IVF – a leading company for IVF and genetic testing – more than 250 couples have used PGD for sex selection since 1995.
Just over a third of the treatments resulted in a pregnancy and 64 per cent of parents wanted a girl.
Suppose genetic screening for sex selection becomes much more widely used. One way to prevent a large imbalance between the sexes would be to tax babies born of the more popular sex and give the proceeds to those who have babies of the less popular sex. The size of the tax could be set at whatever level is needed to achieve a balance between the sexes. That would be a lot easier to enforce than a ban against sexual selection since such a ban would be hard to enforce. Tax collection and disbursement would be a lot easier to carry out. While poor parents would present a problem for any tax collection system the collection side could be progressive and it would still work on the middle class and above.
NIH-funded researchers have identified a gene that appears to be a crucial signal for the beginning of puberty in human beings as well as in mice. Without a functioning copy of the gene, both humans and mice appear to be unable to enter puberty normally. The newly identified gene, known as GPR54, also appears necessary for normal reproductive functioning in human beings.
The study, funded in part by the National Institute of Child Health and Human Development (NICHD), appears in the October 23 issue of the New England Journal of Medicine. GPR54 is located on an autosomal chromosome (a chromosome that is not a sex chromosome). The study also was funded by the National Center for Research Resources and the National Institute of General Medical Sciences, both at NIH.
"The discovery of GPR54 is an important step in understanding the elaborate sequence of events needed for normal sexual maturation," said Duane Alexander, M.D., Director of the National Institute of Child Health and Human Development (NICHD). "Findings from this study may lead not only to more effective treatments for individuals who fail to enter puberty normally, but may provide insight into the causes of other reproductive disorders as well."
Puberty begins when a substance known as gonadotropin releasing hormone (GnRH) is secreted from a part of the brain called the hypothalamus. Individuals who fail to reach puberty because of inherited or spontaneous genetic mutations are infertile.
"The discovery of GPR54 as a gatekeeper for puberty across species is very exciting" said the study's first author, Stephanie B. Seminara, of the Reproductive Endocrine Unit, Massachusetts General Hospital, Boston and a member of the NICHD-funded, Harvard-wide Endocrine Sciences Center. "In the future, this work might lead to new therapies for the treatment of a variety of reproductive disorders."
While the researchers involved emphasize the value of the research in terms of the development of new therapies for infertility there are other less conventional but perhaps more widely useful reasons for being able to control the onset of puberty. Among the very practical reasons to delay the onset of puberty:
As I've argued previously, we need to adjust humanity to be more adaptive to the environmental changes that we have created for ourselves which are a consequence of technological advances. The delay of puberty is a great example of how humans could be made more adaptive to modern industrial society. Humans were already selected for to spend a longer time in childhood learning than is the case for most species. But modern technological society demands an even longer period spent learning than we are designed for. Puberty comes too soon before learning is done and before humans are trained well enough to be able to work and support a family. It makes no sense to have puberty start as soon as it does.
Sperm turn out to do such a great job of packing in and coating their DNA that they can be dried, sealed, and stored at room temperature for use in In Vitro Fertilization (IVF)
Madrid, Spain: A novel method of preserving sperm through air drying is showing initial promise and has the potential to revolutionize sperm storage, allowing men awaiting in vitro fertilization (IVF) to take care of their sperm at home.
Dr Daniel Imoedemhe, a consultant in reproductive medicine and endocrinology, working in Saudi Arabia, told the annual meeting of the European Society of Human Reproduction and Embryology, that for the first time studies on human embryos fertilized with air-dried sperm have shown that the new technique does not impair the early stages of embryo cell division.
Dr Imoedemhe, from Erfan and Bagedo Hospitals, Centre for Assisted Reproduction, Jeddah, said that in the past it was believed that sperm "died" when allowed to dry in air because they were no longer motile and therefore unable to penetrate an egg. "But with the technique intracytoplasmic sperm injection (ICSI), the loss of motility doesn't necessarily mean the loss of ability to fertilize an egg, since this is largely dependent on the DNA (genetic material) that is tightly packed into the sperm head. We believe our study confirms that sperm DNA is resistant to damage by air drying."
Current techniques for freezing sperm are expensive.
Sperm are stored in large liquid Nitrogen tanks that require regular top-ups to ensure that they remain in the desired condition. The tanks are expensive, large and occupy a great deal of laboratory space. In the current system, in order to prevent mis-identification during recovery from storage tanks, a rigorous labelling and coding system is required.
"These methods are time-consuming and cumbersome compared to our simple technique of air-drying that just requires re-suspension before use," said Dr Imoedemhe. "The process can be further simplified by allowing patients to take responsibility for storing their air-dried sperm at home."
The new air-drying technique involves smearing a sample pellet of washed sperm on to a glass slide and then leaving it to dry for two to three hours in a laminar flow cabinet that allows a directional flow of filtered air to ensure that the sample remained uncontaminated by airborne dust or micro-organisms. The dried sperm can then be stored at normal room temperature or in a normal refrigerator and do not seem to require any other special storage conditions. Just prior to injection by ICSI into an egg, the sperm film can be re-suspended with a large drop of special biological medium (similar to that in which the eggs are held in order to avoid osmotic changes).
This technique has not yet been tested using eggs that were of the same quality as the eggs typically used for IVF techniques. Therefore the poorer results with the air-dried sperm are at least partially attributable to the poorer quality eggs used for those experiments.
But although drying did not seem to interfere with fertilization, it was found that 72 hours after sperm injection, the therapeutic group (eggs fertilized with fresh un-dried sperms) had significantly more embryos advancing to the eight or more cell stage than the experimental group (air dried sperm) – 50.5% versus 18.2%.
However Dr Imoedemhe believes this may have more to do with the differences in experimental procedure necessitated by the difficulty of acquiring fresh mature eggs for the experimental group, than the effects of air-drying. In the treatment group all the eggs were mature (at metaphase II), whereas in the air-dried group the eggs were immature (at metaphase I) and had to be matured outside before ICSI. It is thought that such immature eggs may have less potential for development after fertilization compared to normally matured eggs.
If this becomes cheap and easy to do one can easily imagine why some men will arrange to have it done just as an insurance policy against the possibility of disease or injury.
This also opens up greater possibilities for sperm theft. If the sperm can more easily be stored then there will be greater incentive for a woman to get sperm from someone they have a brief affair with and arrange to have the sperm air dryed and then kept for later fertilization. A woman could easily build up a large collection from all the men she ever slept with and then go thru and, once DNA sequencing is cheap, sequence a part of each sample and then choose which man's sperm she wants to use for making a baby on her own.
Update: Dr. Nikolaos Sofikitis, professor of urology at Ioannina University in Greece, has taken germ cells from healthy testicles of men who had testicular cancer in the other testicle and transplanted the germ cells back into the testicular area after cancer treatment was completed. This restored sperm production in the cancer patients.
The new technique preserves the "germ cells" which make sperm, which are frozen and then transplanted back into the man when he is given the all-clear from the disease.
Remarkably, the frozen cells then "re-colonise" the testicle, and start producing enough sperm to allow fertility doctors to extract it from semen.
The germ cells included stem cells and those cells were able to recolonize the healthy testicle.
The germ cells were then thawed and injected back into the healthy testicles of three of the men.
Thirteen months later, the scientists found the testicles had been successfully recolonized with germ cells that produce sperm.
A group of men had sperm samples taken and pictures taken of them. Their sperm was tested and separately they were rated for looks by a group of women. The men judged to be better looking had higher quality sperm on average.
Maria Sancho-Navarro, a researcher at the University of Valencia, said men were generally rated as being attractive if they had "symmetrical" faces.
"The women found that men with symmetrical faces were more attractive. These men had eyes, ears and nose that were more symmetrical than the other men," she told BBC News Online.
This is not too surprising. The ability of women to judge the healthiness of potential mates would have been of considerable selective value. Many problems that occur during fetal development cause asymmetry in the resulting organism. So for humans to find facial symmetry as an important component in judging attractiveness is not surprising.
It would be interesting to know is whether people with symmetrical faces have longer life expectancies.
Also, on a related note, another study found that men who were shown pictures of women to rate their attractiveness and separately heard the same women sing without seeing their faces tended to find the women with the more pleasing voices to have more attractive faces on average. Is the sound of a voice another measure of the quality of embryo development?
The New Scientist coverage of the sperm quality and physical attractiveness study is here.
A new survey discovered 400,000 frozen human embryos in storage in a survey of over 400 US fertility clinics
The freezers of U.S. fertility clinics are bulging with about 400,000 frozen human embryos, a number several times larger than previous estimates, according to the first national count ever done, released today.
Some of the embryos are being retained in storage because the parent owners feel moral qualms about having them destroyed. In other cases the embryos are for future attempts to start pregnancies.
Since an attempt to start a pregnancy with in vitro fertilization (IVF) involves use of drugs to produce 5 to 15 eggs from the ovaries at a time for fertilization and then 3 to 4 embryos are placed in a woman per attempt the number of women involved is only a fraction (a third? a fifth?) of the reported 400,000 embryos.
The article puts the fees charged for embryo storage at $1500 per year. That price places upper bounds on the future popularity of both egg and embryo storage. Still, if a larger and more automated facility could lower those costs by an order of magnitude and if eggs could be stored rather than embryos then it would not be surprising to see affluent young women begin to arrange to have some of their eggs placed in storage so that the eggs would be available for starting pregnancies when they older and less fertile. The biggest argument against doing that is that it seems likely with the current pace of advance in working with stem cells that it will become possible within a couple of decades to create egg cells from stem cells. As new techniques are developed for controlling adult stem cells it seems likely that even they will be able to be converted into eggs. Therefore older women will be freed from the constraint of declining ovarian egg releases.
Preimplantation Genetic Diagnosis (PGD) is done to embryos in vitro to identify embryos which are free of specific genetic disorders. In Vitro Fertilization (IVF) followed by PGD was first performed in 1989 and is now widely available. In Sydney Australia 74 babies have been born who were the result of PGD screening.
A special investigation by The Daily Telegraph today reveals she is one of 74 babies born in Sydney since the genetic screening program began in the late 1990s.
The particular clinic featured in this article, Sydney IVF can currently screen for 37 different genetically caused disorders.
Dr Kylie De Bore, from Sydney IVF, said the service was now available to rural families who previously had to come to Sydney for it. "We can screen for 37 disorders, because families have come to us with that many diseases," she said. "It is not restricted to those."
As the cost of DNA testing declines it seems likely that many people will elect to have tests done on themselves and their mates before conceiving children. There are already many genetic diseases such as Thalassemia, Tay Sachs, Cystic Fibrosis, and Retinitis Pigmentosa which could be avoided thru use of PGD. As the list of known genetic disorders and methods to test for them grow the value of PGD will increase.
Most genetic variations that cause differences in offspring are not diseases. Genetic variations affect eye color, hair color, height, body build, proneness to depression, proneness to obesity, intelligence, personality, and a great many other characteristics about which most people have preferences. We all have characteristics that we have gotten from one of our pairs of chromosomes. When someone reproduces there is currently no way to control which of each pair of chromosomes gets passed along. If, say, someone knew that for their genetic complement only one of a particular pair of chromosomes coded for higher intelligence or a happier disposition one can easily imagine that person would elect to use PGD to make sure that their offspring received the chromosome that coded for the desired feature.
Most people do not have the genetic variations for the big genetic disorders. But everyone who has children has a set of preferences about what they want those children to be like. Therefore it stands to reason that the real big future increase in demand for PGD will come when it can be used to exert some degree of control over the passing along of genetic variations that are not genetic disorders. PGD will therefore become much more popular once the effects of a much larger number of genetic variations become known and testable.
The biggest problem with PGD that will limit its usefulness is that for every trait to be selected for at the same time the number of embryos goes up by a factor of 2 or 3 or 4 (depending on whether it is a dominant or recessive trait and whether each parent has 0, 1, or 2 copies of the desired genetic variation). The number of needed embryos quickly becomes too large for too many different traits.
Scientists hope to improve the technology to the point where it can screen for one, maybe even two, positive 'traits' - for example blue eyes and height. That would still rule out the ideas of the genetic visionaries like Stock, who think PGD could be the first step to 'designer babies' and the re-engineering of mankind, by allowing parents to select among their embryos for all sorts of desirable (to the parents) qualities. The reasons this cannot work are not technical so much as statistical, to do with the way genes are passed on through sex. To screen for two traits you need at least 16 embryos, for three, 64 embryos and so on. Since the maximum number of embryos an IVF procedure produces are typically between 16 and 20, you can do the sums.
What is needed is either the ability to select individual chromosomes by separating them out and choosing which ones to recombine or the ability to do gene surgery to chromosomes to introduce desired genetic variations into an embryo. The gene surgery style of gene therapy is the technique that will ultimately obsolesce the need to generate a large number of embryos with IVF in order to get one that has the desired characteristics. The ability to change the genetic sequences in chromosomes will allow a single IVF embryo to be reshaped to have any desired genetic variations.
Satyabhama Mahapatra, using sperm from her husband Krishnachandra Mahapatra and an egg donated by her niece set a new record for oldest woman to give birth.
Agarwal said Mahapatra had undergone in vitro fertilisation (IVF) treatment at a clinic in Raipur city in the central Chhattisgarh state
She was able to make it only to the sixth month of pregnancy and then the baby was delivered via Caesarean section. Her 26 year old niece Veenarani Mahapatra donated the egg used in the IVF procedure.
But the couple insisted on going ahead with the pregnancy using an embryo from Satyabhama's 26-year-old niece.
While her age still needs to be established she and her husband looked quite old to the doctor who tried to talk them out of trying.
Medical experts are to examine Mrs Mahapatra to try to prove that she is as old as she says. Like many rural Indians, she has no birth certificate, but maintains that she was born in early 1938.
The previous record holder was 63 years old.
Mrs. Rosanna Dalla Corte (ITALY) born in 1931 gave birth to a baby boy on July 18, 1994 when she was 63 years old.
Some day artificial wombs will completely lift the age limit for reproduction. Also, advances in technologies for cloning and for growing replacement organs will eliminate the need to use donor eggs. The ability to grow and implant replacement organs will even allow an old woman to update her reproductive organs to a youthfulness that will allow them to naturally conceive and carry a fetus to term without any need of IVF or even of Caesarean section delivery.
James Watson, president of Cold Spring Harbor Laboratory and co-discoverer along with Francis Crick of the DNA double helix structure, calls for treating stupidity as a disease that should be cured with biotechnology.
“If you really are stupid, I would call that a disease,” Dr Watson said. “The lower 10 per cent who really have difficulty, even in elementary school, what’s the cause of it? A lot of people would like to say, ‘Well, poverty, things like that.’ It probably isn’t. So I’d like to get rid of that, to help the lower 10 per cent.
“It seems unfair that some people don’t get the same opportunity. Once you have a way in which you can improve our children, no one can stop it. It would be stupid not to use it because someone else will. Those parents who enhance their children, then their children are going to be the ones who dominate the world.” Genes that influence beauty could also be engineered. “People say it would be terrible if we made all girls pretty. I think it would be great.”
I'm with James on this one: More smarties and more pretty girls. What a wonderful world it would be.
Tom Shakespeare, a bio-ethicist at Britain's University of Newcastle, criticized Watson's remarks.
"He is talking about altering something that most people see as part of normal human variation, and that I think is wrong.... I am afraid he may have done more harm than good, his leadership of the Human Genome Project and his discovery of 1953 notwithstanding."
Countries where the people do not enhance the intelligence of their offspring are countries that will be left behind. "Naturalists" who do not want to see genetic enhancement of humans are going to be on the losing side in history.
Others think that beauty can not be genetically engineered because it is subjective.
Geneticist Steve Jones, at University College London, dismisses Watson's comments about beauty as "daft". "The concept of beauty is a subjective one," he told New Scientist.
This claim flies in the face of everyday experience. Why do pretty girls get elected home coming queens in high school? Why is there little controversy over who the top contenders are? Why do certain TV and movie stars become the predictable heartthrobs of millions all over the world?
Social science research finds there is a large amount of agreement on what constitutes attractive appearance. (also see this link for the same article)
Men and women generally agree about how attractive another person is, and are often quite accurate in predicting how others will rate their own appearance, new study findings show.
People are going to genetically engineer their kids. They will do this for intelligence, personality, looks, health, and other characteristics. There may well be some countries that pass and strictly enforce laws forbidding this sort of thing. But other countries won't pass the laws or that will not make a concerted effort to enforce the laws. The incentives for genetically enigneering progeny will be so great that people will find a way to do it regardless of what governments say or do.
Update: It may seem hard to believe but some scientists and medical doctors still deny genetics can control the level of intelligence.
Australian Medical Association's ethics committee chairman Dr Trevor Mudge said it was not yet known if intelligence was determined by genetic or environmental factors.
For ideological reasons some highly educated people do not want to admit that genetics is more important than environment in determining intelligence. Obviously toxins and malnutrition can prevent proper brain development. Obviously a mind's development can be messed up by putting a child in an environment in which it can not intellectually develop. But to suppose that environment is the only or even the main factor separating the average 90 IQ person from the average 150 IQ person is ludicrous. Yet as the previous article demonstrates it is still possible to go around and find people with impressive sounding titles and credentials who will deny the role of genetic variations in determining intelligence.
This debate will end when it becomes possible to genetically engineer offspring to be smarter (i.e. probably in about 10 or 20 years). The people who are willing to do genetic engineering to their offspring will stampede to use the biotechnology that does so. Many people who, if asked today, would say they oppose offspring genetic engineering will be first in line to use it when it becomes possible to do so. Many will decide it is so important to give one's own children every advantage that they will place this feeling ahead of whatever argument they advance today in opposition to germ line genetic engineering.
A recent ad quoted in this article offered 15 thousand dollars for a Stanford sperm donor who matched the desired set of qualifications. That's an astounding amount of money for a sperm donation. Egg donations are much harder to make and are riskier for the donors. Hence it is not surprising that prices for Ivy League egg donations can range as high as $50,000. A strong demand for the most preferred kinds of sperm and eggs is driving up prices.
Do a search on the internet and you'll find that there is a significant market for Ivy League egg and sperm donors. One company, Tiny Treasures, located in Massachusetts, offers "Extraordinary Ivy League [Egg] Donors". These are recent women Ivy League graduates who are offering their eggs for $8000 to $15000.
"I think it's unbelievable, and kind of strange, although hard to compare," said Jessica Lucent spokesperson for the New England Cyrobank (sic) Center, located in Cambridge, Mass., when asked to comment on the recent trend of high priced offers for donations.
These prices also provide an indication of how much affluent fertile people will be willing to pay to enhance their own DNA that they pass along to their own genetic offspring. If people are willing to pay more to increase the odds of having smarter children when egg and sperm donors are used then they will certainly be willing to do it when its their own chromosomes that they are passing along.
Keep in mind that while the use of high intelligence sperm and egg donors certainly raises the odds of having smarter children it does not guarantee that outcome. Each person has two copies of each chromosome. When they donate chromosomes via a sperm or egg to make an embryo there is as yet no way to control which of each pair of chromosomes will get donated (except in the case of X and Y chromosomes for sex determination). Once technology is developed to control which of each pair of chromosomes gets donated then much of the uncertainty can be eliminated.
The technology required to do genetic modification to human embryos is being developed. The other part of the puzzle that is still missing is the knowledge of exactly which genes influence intelligence and which alleles of each of those genes will boost intelligence.
On the question of which genes have variations that influence intelligence a lot of scientists are looking for candidates. Here's the abstract to a recent paper by David Comings et. al. of the City of Hope Medical Center that looks at a cholinergic pathway gene whose alleles seem to correlate with intelligence differences.
Cholinergic pathways have been widely implicated in cognition and memory, making the respective genes excellent candidate markers for cognitive abilities. Identification of a possible role of cholinergic receptor genes in humans has been hampered by the lack of reported polymorphisms. The authors identified a common AT 1890 polymorphism in the 3'UTR of the CHRM2 gene. To determine if it was associated with IQ, the authors examined 358 adult males and 470 adult females for a total of 828 adults. The subjects were the parents of twins from the Minnesota Twin and Family Study, a long-term study of the genetics and environmental factors in substance abuse. All subjects in the CHRM2 study were of Caucasian ancestry. All were given the Wechsler Adult Intelligence Scale-Revised (Vocabulary, Information, Block Design, and Picture Arrangement) test. The study was approved by the internal review boards of both the University of Minnesota and the City of Hope Medical Center and all subjects gave written informed consent. Using the SSCP technique, the authors identified a common single nucleotide polymorphism, A 1890T in the 3'UTR of the CHRM2 gene based on accession No. M16404. To assess which variable was more closely associated with the CHRM2 gene, the authors performed a MONOVA using both total IQ and years of education as the dependent variables and the CHRM2 gene as the independent variable for the total set. The total MANOVA (Wilks) was significant at P<0.009. The F-ratio for IQ was 4.12, P<0.017, and for years of education the F-ratio was 5.86, P<0.003. The authors have replicated these findings using a quantitative TDT method developed by Abecasis et al. in 230 parent-child trios from the MTFS. While a marginally significant association was found between CHRM2 and total IQ, after stratifying parental origin of transmission, there was a highly significant association for paternal transmission (P=0.007). Although in need of replication, the authors believe these preliminary results are consistent with a role of the CHRM2 gene in cognitive processes in humans, as assessed by both total IQ and years of education.
As the cost of doing DNA sequencing and SNP testing declines (and see the Biotech Advance Rates category archive for technologies on the horizon that will radically lower costs) the search for genetic variations that influence intelligence will become much easier to do. Because of the rate at which DNA sequencing costs are likely to fall it will surprise me if within the next 10 years we do not know most of the genetic variations that influence intelligence.
Once the cost of DNA sequencing declines and many genetic variations that influence intelligence and personality are identified the market for sperm and eggs will shift away from using attendance at an elite school as a proxy for genetic alleles that code for higher intelligence. Customers will be able to choose based on detailed knowledge of the genetic endowment of each potential sperm or egg donor. A competitive market with more available information will produce choices of donors that more closely match the exact preferences of the customers.
For a review of work in the area of genetic influences on intelligence see Robert Plomin's recent editorial in Molecular Psychiatry entitled "Genetics, genes, genomics and g".
The first article cites the example of ads run in a student newspaper offering Stanford female students $50,000 for egg donation.
The use of egg donors is increasing at nearly 20 percent annually, as more women delay childbearing to the point where their own eggs are in trouble. (If human cloning, which relies on ripe eggs, becomes a reality, it will call for even more donors.) Though some years off, new technology might help. Scientists are finding ways to ripen eggs in test tubes rather than in women's bodies, eliminating the risk of ovary-stimulating drugs. And frozen egg technology will enable women to store their own eggs for later use–rather than look to vulnerable students in search of tuition payments.
This article doesn't explain why most egg sources are cheaper than the Stanford example.
In the United States, prices vary greatly from clinic to clinic, but you should expect to pay between $15,000 and $20,000 for one donor egg or embryo in vitro fertilization (IVF) cycle. This includes the cost of compensation for the donor (usually about $5,000) and one cycle of IVF (usually between $12,000 and $17,000). If your insurance policy doesn't cover this treatment, you'll have to pay the entire cost up front.
Someone who was considering using donor eggs who looked into this market tells me there is a large price premium on higher IQ donor eggs. It is not a coincidence that the advertisement offering such a high price for donor eggs was run in a Stanford newspaper. In order to get into Stanford one has to be exceptionally bright. The Ivy League students get higher price offers to be egg donors as well. The growing use of donor eggs is driving up the price. That $50,000 price is literally a multiple of what it was a few years ago for top quality eggs.
Donor eggs are not a panacea for aging women. Their bodies are less able to support a pregnancy.
However, these successful pregnancies do not come risk free for older women. Even among women in their 50s who had passed a rigorous physical, the study found a 20 percent risk of gestational or pregnancy induced diabetes and a 35 percent risk of preeclampsia or pregnancy related high blood pressure.
The use of donor eggs is not always reported as such.
They make it look easy -- the celebrities who are regularly featured on tabloid covers, appearing to have almost effortlessly had a baby or two when they're beyond their 20s or 30s.
"These are women who are in their 40s, often late 40s, and the tabloids are saying they just had twins. And what they don't say is that these women used donor eggs," says Dr. Michael P. Diamond, director of reproductive endocrinology and infertility at Wayne State University, Detroit Medical Center and Hutzel Hospital.
In the long run technologies for viable creating eggs from cells and the genome of the mother-to-be will be developed. Eventually it will be possible to manipulate adult fully differentiated cells to make them do meiotic cell division to produce eggs. It will even become possible to grow new ovaries from stem cells just as it will become possible to grow other types of replacement organs from stem cells. It is likely that in many cases (depending on each woman's willingness to do so) these techniques will be done in conjunction with gene therapy that fixes any harmful mutations that one doesn't want to pass along to offspring. There will even be gene therapy to modify genetic sequences to produce changes that are enhancements such as higher intelligence or changes in appearance.
This is an intermediate stage technique that will be used until it becomes possible to grow new replacement ovaries:
Collecting ovary tissue from rare animals and growing eggs in other species "could help preserve genetic diversity within endangered species," says one of the researchers, Shae-Lee Cox of Monash University in Clayton,Victoria. It could also speed up livestock breeding, help the study of egg development in exotic species, and even preserve fertility in cancer patients.
Cox and her colleagues grafted sections of mouse ovaries onto rat kidneys. The rats had their immune systems suppressed and so did not reject the tissue. The scientists collected eggs from the ovaries, fertilized them and then implanted the resulting embryos into a surrogate mouse.
Five healthy pups were born from 31 different transplants. All five mice were fertile and went on to produce their own healthy pups.
Researchers Dr. Michael Soules, Dr. Nancy Klein, Dr. Angela Thyer are leading a project at the University Of Washington Fertility and Endocrine Center to develop a technique that within 3 years may allow prediction of how many years of fertility a woman has left:
After puberty, some of these eggs begin to grow and move toward the center of the ovary. The layers of cells that surround these eggs also grow, secreting a liquid as they do. And in that liquid lie the hopes of the project.
The growing egg and surrounding cells are known as antral follicles, and the UW researchers believe there is a correlation between the number of them at any given time and the total number of eggs in the ovary. The more antral follicles, the more eggs remaining. What makes this so important is that the liquid in antral follicles shows up on sonograms.
Soon, doctors may be able to tell a woman how many eggs she has with a simple ultrasound.
The team wants to count another 100 or so ovaries before it draws any conclusions, but the researchers believe that a normal, fertile woman has between 20 and 25 antral follicles at any time. Women with 10 or fewer will have a hard time conceiving.
This result argues for the development of an effective male contraceptive that would shut off spermatogenesis until a man is ready to father children. Note that as sperm progenitor cells go thru each cell division there is a risk of error during the duplication process. So a way to shut down the process until real functioning sperm are needed could greatly reduce the rate at which harmful mutations accumulate:
Importantly, disorders linked to advancing paternal age begin to increase rapidly at about the same time as maternal risks increase -- age 33 to 35. Until now, the only evidence for paternal age effects has come from determining how many children with these diseases are born to fathers of various ages.
To obtain the first genetic explanation for these effects, the scientists studied sperm from about 60 men of various ages and looked for two genetic changes responsible for 99 percent of the cases of Apert syndrome. They found that men over 50 were, on average, three times as likely as men under 30 to have sperm with at least one of these changes. The mutations were not more common in blood samples as men aged.
The scientists say it's likely that the number of cell divisions that go into making a sperm plays a large role in the link between Apert syndrome and paternal age, and represents a fundamental difference between how aging egg and sperm can impact the health of a child.
When a couple decides to have a child they are uncertain what the child will look liike, what sort of personality the child will have, or even whether the child will have inherited genetic defects. The biggest reason for this uncertainty is that each person donates half of their genetic complement to their children but they do not control which half they donate.
The human genome is made up of 23 pairs of chromosomes. One of each pair came from the mother and the other came from the father. Lets call each member of each pair A and B where the A chromosomes are from your mother and the B chromosomes are from your father. So you have chromosome pair 1 and it has members 1A and 1B (1A from your mother and 1B from your father) and the same for the other pairs, 2A and 2B, 3A and 3B, and so on. Well, when you have a child you could donate all your A chromosomes or all your B. Or you could also donate all your B chromosomes. But you could also donate just 1 of your As with 22 Bs or 2 of your As with 21 Bs. So how many possibility combinations can you donate? The number is is 2 to the 23rd power or 8,388,608 unique combinations.
Well, it still takes two people to produce a child and your mate can also donate just as many different combinations. The total possible combinations of genetically distinct children you can have from different chromosome pairings is 8,388,608 times 8,388,608. That's 2 to the 46th power or over 7 to the 13th power or over 70 trillion combinations. This is why two children of the same parents can be so different from each other. In fact, while it is extremely unlikely to happen it is possible for two siblings to have no chromosomes in common. For instance, one sibling could get the A chromosomes of each parent and the other could get the B chromosomes of each parent.
Right now it is difficult and expensive to control which chromosomes get passed along and it is only practical for a single chromosome and only then in extreme cases. Typically it is done to assure that a child will not carry some genetic defect that each parent possesses or to make the child genetically compatible with an existing child which needs a cell donor to treat a genetic disease.
Since the meaning of most genetic differences is not understood at all even if we today had the ability to control which of each chromosome pair we wanted to pass along we wouldn't have any reason to try. We simply don't know enough to choose one chromosome over another except in rather exceptional situations.
So how will control of which chromosomes get passed to offspring affect mate choice? Well, this will be good news for some men who might otherwise be passed over when females are selecting mates.
A Virginia company is now offering a service to separate Y and X chromosome bearing sperm to control the sex of offspring. This technique is not perfectly accurate but it does tip the odds considerably. Also, each try is not guaranteed to result in a pregnancy.
From their FAQ page:
From their Results page:
What is the chance of getting the desired gender?
Currently, MicroSort sperm separation for female gender selection (XSort) results in an average of 88% X-bearing sperm in the sorted specimen. MicroSort sperm separation for male gender selection (YSort) currently results in an average of 73% Y-bearing sperm in the sorted specimen. These data are determined by fluorescence in situ hybridization (FISH) which allows the number of X- and Y-bearing sperm cells to be counted from a fraction of the sorted sample. A child of the desired gender cannot be guaranteed because the current technology does not completely exclude either female or male sperm cells from the enriched sample. Please view the Current Results page and our Journal Publication
The MicroSort Clinic average cumulative IUI pregnancy rate is 17% per treatment cycle. MicroSort IUI pregnancy rate for the year 2000 was 21.5% per treatment cycle.
Pregnancies & Births
As of June 2002, a total of 460 pregnancies have been achieved using MicroSort; 295 babies have been born so far with many more due to deliver.
Microsort's services can be used long distance. A Belgian doctor in Ghent is providing sex selection services using Microsort:
A BELGIAN doctor defended has himself defiantly for offering to allow couples to choose the sex of their child, for a payment of 6,300 euros.
Dr. Frank Comhaire, a professor in fertility problems at the University of Ghent, has already started treating five women from a number of European countries, according to Belga news agency.
According to the article Belgium may soon outlaw this practice. Though if other clinics in Europe started offering it interested Belgians could get around the law. At the extreme they could travel to Virginia and use a clinic near Microsort for the service. An American woman has posted on a web page the breakdown of her costs for using the Microsort technique. Her total cost including tests, travel and hotel was $5,134.00 USD. The Microsort fee was $3,100.00.
There is even a way to increase the probability that the resulting pregnancy will yield the desired sex. In this article in The Guardian a woman reporter posing as a potential client visited Belgian Doctor Comhaire's clinic:
But to do one further check, to make sure through a pre-implantation diagnosis that the embryo is in fact the desired sex, will cost a further €6,000 (£3,800). This will give a '99 per cent chance of success' - for a final price tag of just over £8,000.
and people are willing to cross national borders to use the service:
The customers come from all over Europe, he said - 'from Spain, from Norway, from the UK, from Berlin'. He said several British couples had attended already and had been 'successful' - but he would not divulge their numbers or how many were pregnant.
Humans have been engaged in a crude form of genetic engineering for as long as they have been a species. Every time a man chooses a woman and a woman chooses a man for the purpose of reproduction they are (consciously in some cases; not consciously in others) choosing characteristics in the other that are attractive for them to have in their offspring. Humans are attracted to qualities (eg symmetry of shape, strength, healthy looking skin, etc) in potential mates that bode well for having healthy successful offspring.
What are the major types of drawbacks in our current ways of passing along our genes to our progeny?
• We don't know what problems exist in our own personal genomes.
• We don't know what particularly beneficial variations we each might have.
• We don't know what of our own genetic endowment we are going to pass along.
• We don't know what our mates or potential mates have in their genomes or what they will pass along.
The result is uncertainty and sometimes tragic surprises. Two seemingly healthy people can give birth to a child that gets a recessive bad gene from both parents and therefore has a genetically caused disorder.
Abilities and knowledge that we need:
• To know the exact sequences we each individually have in our own genomes.
• To know what each variation means and therefore to be able interpret our own genomes.
• To be able control which of our chromosomes we pass along.
• To be able to change the genetic sequences what we pass along to give our progeny variations we don't have.
Humans have been using (consciously or not) methods of identifying potential mates with good genetic endowments for as long as the human race has existed. Many attributes of physical appearance, ability to tell jokes, prowess in sports and fighting, demonstrated personality characteristics such as patience or assertiveness, and still other characteristics have been used by males and females to judge each other since our species came into existence. Ancient religious texts even provide guidelines for choosing mates.
These methods are far from perfect. There are lots of reasons for this. Some qualities of a person may not manifest for many years (eg a genetic defect may give them a neurological disorder in their 30s or a heart attack in their 40s). It gets even more complicated. Some qualities will not ever manifest in the parents but will show up in some or all offspring. Two perfectly healthy looking people can both harbor a recessive harmful genetic mutation and can have offspring which suffer from any of a number of illnesses caused by such mutations (eg Tay Sachs). Or two who chose to become mates could have immune system weaknesses that never killed them since they never encountered a pathogen for which they are genetically poorly equipped to fight and then their offspring could encounter the pathogen and some or all of the offspring may die from it. The same can hold for other challenges that the environment throws up which do not happen for every generation.
But the problems with mating are even greater than that. Look at how much different children of the same parents can differ. Take some of the qualities that many women are attracted to in men: success in fields that require mental and or physical skills such as pro athletics, popular music writing and performance, science, or high status roles in government and industry. Just because a woman mates with a man who is enormously successful in some occupation does not mean that the resulting offspring will be equally capable of being successful in that or other high status and high income occupations.
Future advances in biotechnology will increase our ability to predict the outcomes of potential matings and even eventually to control exactly which part of our genomes we pass along to our offspring. Much of the uncertainty about what sort of offspring we will have will be removed. Not only will the uncertainty be removed but we will gain considerable control over what characteristics we pass along. Eventually biotech will allow us to go even farther and to give our offspring genetic variations that we do not ourselves possess.
I'd like to go thru the logical steps of how genetic engineering techniques of offspring is likely to progress. Keep in mind that the logical steps are in order of increasing power of the techniques. These are techniques for changing the genetic endowments of future generations. While I'll cite some examples of how this will change the resulting offspring it is beyond the scope of this essay to enumerate all the ways that people will become different than they otherwise would have been.
While I'm going to describe successively more powerful techniques it is possible that some of the more powerful techniques may become available before some of the less powerful techniques. The ordering of the techniques is in order of much much the techniques can change us and not the order in which the techniques will become available. So while I view control of chromosome donation to be a less powerful technique that gene therapy on fertilized eggs it may well turn out to be the case that gene therapy on fertilized eggs will become possible before chromosome donation can be controlled.
Also, just because a technique becomes available does not mean that people will use it. There will inevitably be people who will find moral or other reasons to reject the use of some or all of these techniques. So the order here is not necessarily the order in which the techniques will become either possible or acceptable.
Also, each technique will first become available in less powerful partial implementations and later in more powerful implementations that allow the full theoretical benefits of the general technique. For example, the first logical step of genetic profiling will start out with a small number of testable genetic locations for particular genetic diseases (this is already the case with Tay Sachs and other genetic disorders). Only gradually with time will it become sufficiently fast and cheap to allow each person to get all of the genetic variations of their genome mapped in complete detail. So the initial use of genetic profiling will give one an only partial picture of oneself and one's potential mate(s). Also, the initial high cost for each step will initially restrict the number of people who use each technique and as costs fall each technique will spread into more widespread usage.
First a listing of the steps in advances in genetic engineering techniques:
• Step 1: Screen potential mates or potential DNA donors (eg egg donors or sperm donors) by genetic profile.
• Step 2: Select which of each pair of our chromosomes we pass on to our progeny.
• Step 3: Assemble chromosome sets from more than 2 people.
• Step 4: Gene therapy on eggs, sperm or fertilized eggs.
• Step 5: Build chromosomes by combining genetic variations from chromosomes of many people.
• Step 6: Introduce genetic variations new to the human race.
• Step 7: Introduce genes from other species
• Step 8: Create entirely new genes
As you can see the first logical step will simply refine our methods of mate selection. We will simply know more about potential mates from a genetic perspective. But then we will gain successively more control over what our progeny will receive as the genetic structure in all of their bodies. As an aside we will discuss gene therapy that takes place on the egg or sperm or fertilized egg with the goal of permanently affecting the entire resulting person. While we will also gain the ability to use gene therapy to change the genetic structure of subsets of our cells that topic is outside the scope of this essay.
So this brings us to our first step forward into a Brave New World:
Once genetic sequencing becomes very cheap and widely available everyone will be able to know their exact genetic sequence. Any and all genetic variations that contribute to appearance, health risks, and ability for various types of sports, music composition, mathematics, and assorted other pursuits will be identified. How will this change the mating game? Initially I foresee dating/mating services where people register and provide their genetic profile (this could be done with some anonymity so that the service doesn't know which real life individual has which profile btw). Along with a genetic profile someone could submit a "what I want in a mate" genetic profile that would consist to absolute requirements for variations in some genes and preferences for variations in other genes.
The ability to search rapidly thru large numbers of other people to look for preferred characteristics will lead people to take a much more critical look at potential mates. Imagine a woman named Sue has a choice between two males named Bob and Joe that outwardly are very similar. They have similar levels of intelligence, looks, risks for diseases, and other qualitiies. But while Bob and Joe both have straight shiny teeth at the genetic level they are not the same. Suppose the gene for this characteristic (I'm making this up as example though surely there are genes that code for teeth shape) acts as a classical Mendelian dominant. Whether you have one or two copies as long as you have at least one copy of it you get the outward characteristic. Lets assume Bob has 2 copies of the straight shiny tooth gene while Joe has just one copy of the straight shiny gene along with a recessive not-nice-looking tooth gene variation). Joe has teeth that look as good as Bob's. But there is an important difference when it comes to offspring. Sue has just one copy of the good tooth gene. So if Sue mates with Joe each kid will have a 1 in 4 chance of having bad teeth (a child would have get a bad tooth gene from both parents and that will happen on average once every 4 kids they have). But if Sue mates with Bob no matter what tooth gene Sue donates to her children Sue can be secure in the knowledge that Bob will donate a good tooth gene (since Bob has only good tooth genes to donate). Both of Bob's copies are what Sue wants and so Sue has a better chance of having kids with great teeth if Sue goes for Bob.
This stage of advance in mating will be most advantageous for women who aren't looking for a husband. Women who are just looking for sperm donors won't need to be attractive to the men who might donate. The men don't need to sign up to raise kids with the women who are looking for sperm donors. So a single woman who wants to raise a kid on her own will be able to search all the sperm donor banks and choose a donor with a much clearer idea of what she will be getting.
Okay, suppose you are a woman who has just chosen the best mate your genetic profile could attract from the genetic profile dating service. Or maybe you fell in love the old fashioned way. But still, you know your own genetic profile and that of your mate. Your mate has a variation of some gene you desire to pass on to your offspring (lets say red hair). But the lug only has that gene on one chromsome of his pair of chromosomes that carry the hair color gene (and, again, this is a simplication for the sake of illustration; there might be multiple genes controlling hair color). You have only a 50:50 chance that he'll pass the desired gene on to your offspring (and you so want the kid to have red hair just like you and your mother before you). For most of human history you just had to roll the dice, get pregnant, and hope for the best. But eventually biotech advances will let you fix the dice and control which of each pair of chromosomes each of you donate to your offspring.
The ability to exercise this control will actually relax mate choices. Someone with undesireable genetic variants on one chromosome and desireable genetic variants on another chromosome of the same chromosome pair will no longer be shunned by the choosiest mate hunters. Only the most desireable chromosome of each chromosome pair of each potential mate will matter. The worse member of each chromosome pair will be avoidable in offspring.
Aside for those who know that DNA crossover during meiosis complicates this picture: I'm assuming that a drug will be developed that can suppress that from happening.
Okay, you can't find your perfect mate. Plus, you have some genes on both members of a chromosome pair that you don't want to pass on to your offspring. But you think one of your chromosomes is so great you want your kid to get both copies of it. What you need is total control over which chromosomes of yours and of one or more other people you want to use to construct your offspring.
Basically, some manipulation technique will lift the requirement that each parent donate exactly one of each chromosome pair to offspring. For one particular pair you might not donate anything. For another pair you might donate both. Once that basic capability of pulling out particular chromosomes and assembling your choices together is possible then it will be no harder to do with with chromosomes selected from 5 people than with chromosomes selected from 2 people.
This will be a big step forward in the ability to optimize the genetic endowment of offspring. Combinations of chromomes that can not be assembled from any two pair of existing people will be able to be put together. Outcomes that previously would haven taken multiple generations will now be achieveable in a single generaiton.
Staying within the range of variations that humans naturally have go into a fertilized egg (or the egg or sperm before fertilization) and modify the DNA to change a gene. In some cases this will be done to prevent children from receiving a defect that their parents have. However, it could also be done to give one's children features that the parents don't possess that other people possesss. This could be done for reasons that range anywhere from cosmetic (red hair or green eyes or greater height) to rather substantial things such as a personality type or greater coordination or muscles that could be developed to make someone a natural sprinter.
For people carrying genetic defects the prospect of gene therapy will be seen by many as extremely beneficial. Suppose, for instance, a couple both carry genes for hemophilia (where the blood doesn't clot properly). They may want to have children that do not carry the genetic defect that they carry. So gene therapy done at a very early stage of fetal development could change the DNA of the fetus so that the child will grow up free of the defect of the parents and will even be able to have children that do not have the defect.
The limitation of gene therapy (step 4) on the early stage of development is that its hard to use it to introduce a large number of genetic changes. At the same time, the ability to assemble sets of chromosomes by taking chromosomes from more than 2 people (Step 3) is still limited by what combinations of genetic variations can be found on individual existing chromsomes of all the people in the human race.
You may choose a set of features that you want your child to have that all are controlled by genes on a particular chromosome. But there may be no existing copy of that chromosome that has the particular combination of those features that you desire.
There's another reason why it will desireable to do larger scale changes to chromosomes. Some genetic theorists believe that we each carry dozens or even hundreds of deleterious mutations (we don't all carry the same deleteriousl mutations and some of the harm from these mutations manifests in rather mild ways). Every person on every chromosome may have mutations that are harmful to them. Well, we really need to be able to get into each chromosome and basically scrub it clean of deleterious mutations.
The average human being's health and general abilities can rise very dramatically just by sorting thru the genetic variations that already exist among humans. There are literally millions of locations in the DNA that vary from one person to the next. Many of those variations have no effect on us. Some variations are in silent areas of the genome. Still other variations are in used areas but don't cause any functional changes. Still, estimates for the number of significant differences in human DNA start at around 100,000 and range upward from there.
Scientists are already trying to sort thru the genetic differences between people to find out what effects they have. As the meanings of these differences become elucidated we will be able to make more intelligent choices about which existing variations we want to pass long to our offspring. This alone will cause a large change in the average of the human race as poeple make different choices about the height, appearance, personality types, intellectual abilities, and risk of diseases that their children will have.
But at some point scientists will begin to discover ways to improve upon the sum total of all the existing human variations. These ways to improve upon existing human designs may well occur years before all the existing variations are fully understood. But I'm placing them here as later steps just to make clear that they represent a further logical step in the progression of types of genetic engineering that will be done to humanity.
Steps 4 and 5 can be done with genetic variants that exist in the human population. However, more advanced genetic engineering will involve the introduction of new genetic variations that do not now exist in humans. Some of those variations and genes will come from other species. Still others will be designed by trying out or simulating variations of existing structures to see if the variations yield desired improvements in functionality.
Some of what will be done here is to take human existing genes and the proteins that get made from them and to run computer simulations that show how the genes and proteins would function if each position in the gene was changed to other letters in the genetic code. By trying variations that have not yet occurred naturally it will be possible to find for improvements over the variations that already exist.
This step does not involve introducing new genes. It just involves changing the genetic letters in positions of the genetic code of existing genes. However, as we can clearly see by looking at the enormous range of variations in existing humans even this approach can produce dramatic differences between humans.
Since other species contain many of the same genes as humans do and with very similar sequences one place to go looking for promising variations is in other species. However, other species also contain genes that humans do not have. This brings us to our next step.
A more radical way to get improvements is to look for genes to use in humans that come from other species of plants, animals and even from single cell organisms such as bacteria. The advantage of looking at other organisms for improvements is that so many organisms have had to survive in so many kinds of environments and they have adaptations that probably just never had a chance to arise in humans. So there are lots of well tested genes in other species that are worth examining to look for useful parts.
There are scientists looking at bacterial DNA repair enzymes with an eye toward putting them in humans to slow DNA damage accumulation that accompanies aging. There are also scientists looking at bacterial enzymes that break up waste products that accumulate in cells. One goal would be to insert the genes for these enzymes into human cells so that the lipofuscin and other compounds that accumulate with age could be broken down.
Still another way to try to improve the human species is to try to come up with entirely new and novel genes which code for proteins that do things not found in humans or other organisms. This is harder than trying to improve on existing designs and is also harder than looking for better designs in other species. But eventually bioengineering will advance to the point where this becomes possible as well.
The 21st century will see an acceleration of the rate of change in the human genome to a speed many orders of magnitude faster than what has been its historical rate of change. Some of the early stages of the change will not seem superficially so dramatic because people will initially just select among existing variations. Future generations will be chosen to be more attractive, healthier, and with the most desired intellectual and personality characteristics. However, as bioengineering advances new types of genetic variations and genes from other species will lead to still greater changes in humanity.
People will have many motives for genetically engineering their children and many types of changes that they will desire to introduce into their children's genomes. In future posts I will explore in greater detail all the different categories of modifications that people will decide that they want to make in their progeny. Another incredibly important topic to be explored in future posts is the question of whether genetic engineering could lead to offspring who have characteristics that literally threaten the fabric of civilization.