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 in what they tell us egg donors with sought after genetic profiles will find that banking lots of frozen eggs very profitable. I expect top egg donor prices to go 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 for much more when their genetic profiles show they offer much higher odds for giving prospects parents what they want in their children.
In Vitro Fertilization accounts for at least 1% of births in the United States of America.
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.
Lesbian sexual reproduction keeps getting closer.
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.
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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.
The existing IVF procedure requires 5 weeks of taking powerful and potentially dangerous drugs.
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.
Does the FDA really think that imported sperm create a risk of spreading Creutzfeldt-Jakob disease?
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.
Preimplantation genetic diagnosis (PGD) does not boost the risk from in vitro fertilisation (IVF).
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.
Lower hormone doses reduced the number of genetically damaged embryos produced.
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.
Beyond age 35 the odds of conception go down rapidly.
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.
An embryo frozen for 13 years was used to start a successful pregnancy.
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.
A company stands ready to offer services using these results.
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.
Lapascopically extracted cells from human ovaries can be turned into viable eggs.
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.
You can read the abstract for the research paper or the full research paper (the latter is PDF format).
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.
Her 33 week pregnancy was over 6 weeks short of a full 40 week pregnancy.
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.
The pregnancy started out with triplets but only one made it.
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.
After two of the fetuses died a Caesarean was done.
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.
Arryx has developed a device that can move movement of microscopic objects using lasers.
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.
Cow semen sorting by sex chromosome will be available in 2005.
"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.
Background information on Grier's laser tweezer work is available on his web site.
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 in