A 21-YEAR-OLD Frenchman is the first person in the world to be cured of the blood disorder beta-thalassaemia through gene therapy. But there is some confusion over what made the treatment work.
Before gene therapy he needed monthly blood transfusions to provide him with beta-globin, a key component of the haemoglobin molecule that carries oxygen around the body. He has now been transfusion-free for over two years.
Philippe Leboulch of the University of Paris, France, and Harvard Medical School in Boston, infected stem cells from the man's bone marrow with a harmless virus, which transferred perfect copies of the beta-globin gene into the DNA of the extracted cells.
Returned to the patient, these cells now contribute about a third of his beta-globin, with his body producing the rest. Although the treatment had the desired effect, the proliferation of the altered cells could be down to the activation of a different gene, HMGA2, switched on by accident during the DNA transfer.
One worry throughout the history of gene therapy is that viruses transferring beneficial genes will accidentally activate other genes that could trigger cancer. This happened in four French boys treated for the immune deficiency, X-SCID, who developed leukaemia. One died and the others recovered after treatment.
"We must be very cautious, but the signs are that the impact of the HMGA2 gene will be benign," says Leboulch.
After more detailed analysis, the team found other cells producing beta-globin that do not have the HMGA2 gene switched on. Leboulch concludes that it is unlikely the HMGA2 gene by itself is responsible for the survival of the beta-globin-producing cells.
Tuesday, September 7, 2010
Monday, September 6, 2010
Doctor sued over allegedly mixing up sperm samples
An Ottawa fertility doctor is being sued for allegedly mixing up sperm samples and inseminating the wrong one into two of his patients.
Trudy Moore launched a civil lawsuit against Bernard Norman Barwin last year after she learned that her daughter, Samantha, is not a genetic match to her husband, Matthew Guest, the statement of claim said.
Recently, another woman also came forward and filed a statement of claim against Dr. Barwin. Jacqueline Slinn found out in April that her five-year-old daughter Bridget is not a genetic match to her intended sperm donor, the statement said.
Both women are seeking more than $1-million in damages and an order requiring Dr. Barwin to identify their children’s father. No mediation or court dates have been set.
“We are currently investigating how widespread this problem may be,” said Pam MacEachern, lawyer for Ms. Moore and Ms. Slinn. “We would be pleased to speak with anyone else who has had a similar experience.”
In a statement of defence filed by Dr. Barwin in response to Ms. Moore’s lawsuit, he denied any allegations of negligent care or wrongdoing. The claim states that all medical care and treatments provided were carried out in a careful, competent and diligent manner and in accordance with the applicable standard of care.
Dr. Barwin and his lawyer could not be reached for comment.
According to Ms. Slinn’s statement of claim, Bridget’s father was supposed to be sperm donor number 3168. After Ms. Slinn learned that her daughter did not match him, she tested the vial of sperm that was used to inseminate her from Dr. Barwin’s clinic. The results showed that the vial from his clinic was contaminated with unidentified male DNA, the statement said.
In an interview, Ms. Slinn said she had no idea that there was even a risk of that kind of mistake when she went into her procedure nearly six years ago. “I carried on merrily thinking it was 3168,” she said.
Ms. Moore’s story is more complex. Now two-year-old Samantha was conceived through a surrogate, and the man she calls “daddy” is supposed to be her biological father. But due to the mix-up at Dr. Barwin’s clinic, her parents still don’t know who Samantha’s biological father is, the statement said.
“From Samantha’s perspective, we don’t know her medical history,” Ms. Moore said in an interview. “She may never care, but if she does I can’t fix that. As a parent we want the best for our children, we want to protect our children, we want to fix things for our children. This is something I will never be able to give her.”
DNA tests have ruled out the surrogate’s husband and other potential sperm donors.
Dr. Barwin is a member in good standing with the College of Physicians and Surgeons and is certified to practice as a general physician. He specializes in reproduction and has nearly 30 years of experience. In 1997, he received the Order of Canada for his contributions to women’s reproductive health.
Trudy Moore launched a civil lawsuit against Bernard Norman Barwin last year after she learned that her daughter, Samantha, is not a genetic match to her husband, Matthew Guest, the statement of claim said.
Recently, another woman also came forward and filed a statement of claim against Dr. Barwin. Jacqueline Slinn found out in April that her five-year-old daughter Bridget is not a genetic match to her intended sperm donor, the statement said.
Both women are seeking more than $1-million in damages and an order requiring Dr. Barwin to identify their children’s father. No mediation or court dates have been set.
“We are currently investigating how widespread this problem may be,” said Pam MacEachern, lawyer for Ms. Moore and Ms. Slinn. “We would be pleased to speak with anyone else who has had a similar experience.”
In a statement of defence filed by Dr. Barwin in response to Ms. Moore’s lawsuit, he denied any allegations of negligent care or wrongdoing. The claim states that all medical care and treatments provided were carried out in a careful, competent and diligent manner and in accordance with the applicable standard of care.
Dr. Barwin and his lawyer could not be reached for comment.
According to Ms. Slinn’s statement of claim, Bridget’s father was supposed to be sperm donor number 3168. After Ms. Slinn learned that her daughter did not match him, she tested the vial of sperm that was used to inseminate her from Dr. Barwin’s clinic. The results showed that the vial from his clinic was contaminated with unidentified male DNA, the statement said.
In an interview, Ms. Slinn said she had no idea that there was even a risk of that kind of mistake when she went into her procedure nearly six years ago. “I carried on merrily thinking it was 3168,” she said.
Ms. Moore’s story is more complex. Now two-year-old Samantha was conceived through a surrogate, and the man she calls “daddy” is supposed to be her biological father. But due to the mix-up at Dr. Barwin’s clinic, her parents still don’t know who Samantha’s biological father is, the statement said.
“From Samantha’s perspective, we don’t know her medical history,” Ms. Moore said in an interview. “She may never care, but if she does I can’t fix that. As a parent we want the best for our children, we want to protect our children, we want to fix things for our children. This is something I will never be able to give her.”
DNA tests have ruled out the surrogate’s husband and other potential sperm donors.
Dr. Barwin is a member in good standing with the College of Physicians and Surgeons and is certified to practice as a general physician. He specializes in reproduction and has nearly 30 years of experience. In 1997, he received the Order of Canada for his contributions to women’s reproductive health.
Sunday, September 5, 2010
Hull IVF unit innovation is to be rolled out across UK
Technology used in fertility treatment which has been adopted by Hull's IVF unit is being rolled out across the rest of the UK.
The unit has also been nominated for a national award for use of the technology.
The technology lessens the risk of a mix up when the sperm and egg are put together by activating an alarm.
It was designed following highly publicised adverse incidents across the UK.
The unit said IVF mix-ups were rare but in recent years there had been four "highly publicised serious adverse incidents" in UK clinics.
It said two involved incorrect identification of sperm samples and resulted in the live birth of twins.
As a consequence the Human Fertility and Embryology Authority (HFEA) - the UK's independent regulator overseeing the use of gametes and embryos in fertility treatment and research - introduced a requirement for all movement of sperm, eggs and embryos during any clinical or laboratory process to be witnessed to prevent mismatches.
The technology works through a tracking process ensuring that the resulting embryo is transferred to the correct patient.
If at any time the wrong samples are introduced, the system warns the laboratory personnel both visually and audibly.
A spokeswoman for the unit said: "The system provides an invaluable reassurance for patient's nurses and embryologists alike."
The clinic, which is based at Hull Royal Infirmary, has been nominated for the Best Use of Technology category at the the Independent Health Care Awards. The winners will be announced on 14 September.
According to the Hull IVF Unit 37,000 women undergo fertility treatments in the UK every year.
The unit has also been nominated for a national award for use of the technology.
The technology lessens the risk of a mix up when the sperm and egg are put together by activating an alarm.
It was designed following highly publicised adverse incidents across the UK.
The unit said IVF mix-ups were rare but in recent years there had been four "highly publicised serious adverse incidents" in UK clinics.
It said two involved incorrect identification of sperm samples and resulted in the live birth of twins.
As a consequence the Human Fertility and Embryology Authority (HFEA) - the UK's independent regulator overseeing the use of gametes and embryos in fertility treatment and research - introduced a requirement for all movement of sperm, eggs and embryos during any clinical or laboratory process to be witnessed to prevent mismatches.
The technology works through a tracking process ensuring that the resulting embryo is transferred to the correct patient.
If at any time the wrong samples are introduced, the system warns the laboratory personnel both visually and audibly.
A spokeswoman for the unit said: "The system provides an invaluable reassurance for patient's nurses and embryologists alike."
The clinic, which is based at Hull Royal Infirmary, has been nominated for the Best Use of Technology category at the the Independent Health Care Awards. The winners will be announced on 14 September.
According to the Hull IVF Unit 37,000 women undergo fertility treatments in the UK every year.
Saturday, September 4, 2010
Chemical patterns on DNA mark out obesity genes
Your genes play a big part in determining your body shape, but that role may not have been set in stone when your parents' egg and sperm got together. It now looks like chemical changes that happen to genes over a person's lifetime may influence how fat they become, without altering their inherited DNA sequences.
This is the first time that prolonged chemical changes to genes during life have been implicated in obesity and body weight.
The findings add to the mounting evidence that it's not only genes that dictate important bodily traits – environmental cues and conditions may also affect such traits by altering gene activity. These "epigenetic" changes influence whether genes are on or off, but do not change the DNA sequence.
The latest findings relate to epigenetic changes which involve methylation, the process by which the addition of chemicals called methyl groups to DNA can turn genes on or off, or moderate a gene's activity by changing the way it is read.
Icelandic obesity
A team led by Andrew Feinberg of Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniele Fallin of the Johns Hopkins Bloomberg School of Public Health, also in Baltimore, mapped methylation in the DNA of 74 adults with a range of body types, looking for patterns that seemed likely to have been prolonged and set early in life, or even in the womb.
To do this, they first screened the volunteers' DNA in 1991, and picked out 227 regions with methylation patterns that varied between the individual members of the group by an unusually large amount. They then screened the same people in 2002 to distinguish which methylation patterns had not changed over the 11 years, reasoning that the variation in these patterns must have occurred early in life, then become fixed, having a persistent effect on traits such as body weight or intelligence.
Of the 227 methylated sites, 119 were found to be the same in 2002 as they had been 11 years earlier. Feinberg and Fallin then matched these groups to the body type of the individual. They found 13 methylated genes that were more likely to be present in the participants who were overweight or obese.
These chemical changes could have arisen in response to environmental conditions, such as the childhood diet of the individual or even of their mother during pregnancy.
"We don't know yet the degree to which genes and environment add up to give these stable methylation changes, but we believe both are important," says Feinberg.
Usual suspects
The 13 methylated genes include those that make metalloproteinase enzymes, which have already been implicated in obesity through studies on mice. Another, called PRKG1, plays a role when insects and nematodes forage for food.
The researchers caution that it is not yet possible to say whether the methylation changes are a result of environment influence, perhaps in the diet, or whether they are ultimately genetic because they are orchestrated by other genes.
But if specific methylated genes linked with obesity can be identified, they may provide new ways to screen people for risk of becoming overweight or obese. "The results do suggest the importance of including epigenetic analysis with genetic analysis in personalised medicine research to predict risk," says Feinberg.
"Relationships between epigenetic markers such as methylation patterns and particular disease or body states are hard to establish with confidence," says Bryan Turner, a geneticist at the University of Birmingham, UK.
This is the first time that prolonged chemical changes to genes during life have been implicated in obesity and body weight.
The findings add to the mounting evidence that it's not only genes that dictate important bodily traits – environmental cues and conditions may also affect such traits by altering gene activity. These "epigenetic" changes influence whether genes are on or off, but do not change the DNA sequence.
The latest findings relate to epigenetic changes which involve methylation, the process by which the addition of chemicals called methyl groups to DNA can turn genes on or off, or moderate a gene's activity by changing the way it is read.
Icelandic obesity
A team led by Andrew Feinberg of Johns Hopkins University School of Medicine in Baltimore, Maryland, and Daniele Fallin of the Johns Hopkins Bloomberg School of Public Health, also in Baltimore, mapped methylation in the DNA of 74 adults with a range of body types, looking for patterns that seemed likely to have been prolonged and set early in life, or even in the womb.
To do this, they first screened the volunteers' DNA in 1991, and picked out 227 regions with methylation patterns that varied between the individual members of the group by an unusually large amount. They then screened the same people in 2002 to distinguish which methylation patterns had not changed over the 11 years, reasoning that the variation in these patterns must have occurred early in life, then become fixed, having a persistent effect on traits such as body weight or intelligence.
Of the 227 methylated sites, 119 were found to be the same in 2002 as they had been 11 years earlier. Feinberg and Fallin then matched these groups to the body type of the individual. They found 13 methylated genes that were more likely to be present in the participants who were overweight or obese.
These chemical changes could have arisen in response to environmental conditions, such as the childhood diet of the individual or even of their mother during pregnancy.
"We don't know yet the degree to which genes and environment add up to give these stable methylation changes, but we believe both are important," says Feinberg.
Usual suspects
The 13 methylated genes include those that make metalloproteinase enzymes, which have already been implicated in obesity through studies on mice. Another, called PRKG1, plays a role when insects and nematodes forage for food.
The researchers caution that it is not yet possible to say whether the methylation changes are a result of environment influence, perhaps in the diet, or whether they are ultimately genetic because they are orchestrated by other genes.
But if specific methylated genes linked with obesity can be identified, they may provide new ways to screen people for risk of becoming overweight or obese. "The results do suggest the importance of including epigenetic analysis with genetic analysis in personalised medicine research to predict risk," says Feinberg.
"Relationships between epigenetic markers such as methylation patterns and particular disease or body states are hard to establish with confidence," says Bryan Turner, a geneticist at the University of Birmingham, UK.
Friday, September 3, 2010
Is spring the secret of success for struggling IVF couples?
In the animal kingdom, spring is the mating season. Now scientists claim the same is true for humans.
They have discovered that couples trying for babies with IVF are more likely to conceive in spring than at any other time of year.
Those who had treatment in March, April or May were one-and-a-half times more likely to be successful than those trying during other months.Experts believe that the increase in light in spring could trigger women’s bodies to produce greater amounts of the sex hormone estradiol, crucial for the fertilisation of the egg and development of the embryo.
Scientists from the Assisted Fertilization Center in Sao Paulo, Brazil looked at almost 2,000 women undergoing IVF treatment during all four seasons of the year.
They found that rates of fertilisation – when the egg and sperm join together to make an embryo – and levels of estradiol in the women’s blood were significantly higher in spring.
Dr Daniela Braga, who led the study, suggested that changing light levels caused neurons in women’s brains to produce certain hormones which in turn increased the amount of estradiol produced by the ovaries.
‘This work shows that IVF cycles may have a better outcome during the spring,’ she said.
‘Our results show a significant difference in spring fertilization rate, with the fertilization
rate in the spring being almost one-and-a-half-times that of other seasons.
‘In practical terms this may mean that if you are having real difficulty in conceiving, it may be better to have an assisted reproduction cycle during this season.
‘We found higher estradiol levels in the spring. In assisted reproduction, adequate estradiol levels are important for egg maturation and other reproductive processes including fertilization and embryo development.’
The scientists now want to test if women are more likely to conceive in areas of Brazil nearer the equator, where there is more light.
Their findings back up work carried out by British scientists that showed that fertility treatment was more likely to be successful in spring or summer.
A team from Countess of Chester Hospital and Liverpool Women’s Hospital found that 20 per cent of IVF cycles from May to September resulted in a successful pregnancy, compared with 16 per cent for the remainder of the year.
These researchers suggested that this was down to humans showing the same biological processes as those that occur in birds and mammals.
Thursday, September 2, 2010
Hormone melatonin improves egg quality in IVF
Women with poor egg (or oocyte) quality could double their chance of becoming pregnant through IVF if given melatonin, researchers have found.
'Despite great advances in assisted reproductive technology, poor oocyte quality remains a serious problem for female infertility', said Professor Hiroshi Tamura from the Yamaguchi University Graduate School of Medicine, Japan, who led the research. 'So far no practical and effective treatment for improving oocyte quality has been established'.
High levels of oxidising agents - a type of chemical compound - in the follicular fluids surrounding the egg indicate if a woman has low quality oocytes. These can 'stress' and damage the oocyte. The team took one of these agents known as8-OHdG and measured its levels in follicular fluid samples. Levels of melatonin, which is known to have anti-oxidising effects, were also measured.
The team found that, as melatonin concentration in the follicular fluids naturally increased, the level of 8-OHdG decreased, leading them to believe melatonin was linked to the reduction of the oxidising agents. They confirmed this finding in mice, and discovered that adding melatonin seemed to reduce the damage to the egg caused by the agents.
Next, the group set up a trial with women coming for IVF treatment at the Yamaguchi University Graduate School of Medicine to see if these findings could have real-world effects on IVF. Women who had failed to become pregnant because of poor oocyte quality after one cycle of IVF were split into two groups - 56 women were given three milligrams of melatonin before the next IVF cycle, and 59 just received a standard IVF cycle without melatonin.
The team found that melatonin treatment significantly increased melatonin concentrations in the women's follicles and significantly decreased concentrations of the damaging 8-OhdG. Their results showed 50 per cent of the eggs from women who taken melatonin could be successfully fertilised, as opposed to 22.8 per cent in the control group. When the eggs were transplanted into the womb, 19 per cent (11 out of the total 56) of the women became pregnant, as opposed to 10.2 per cent (six out of total 59) in the control group. The work was published in the Journal of Pineal Research.
'This work needs to be confirmed, but we believe that melatonin treatment is likely to become a significant option for improving oocyte quality in women who cannot become pregnant because of poor oocyte quality', said Professor Tamura. 'Our next step is to analyze exactly how reactive oxygen species harm the oocyte, and how melatonin reduces oxidative stress in the oocyte'.
Professor Russel Reiter from the UT Health Science Center, San Antonio, Texas, who co-authored the paper, agreed. 'it is important that this work be independently confirmed on larger numbers of subjects'. But he added that the findings 'make perfect sense', as melatonin has been shown to protect many different cells and tissues from oxidative damage - the same type of damage known to occur to oocytes.
'Despite great advances in assisted reproductive technology, poor oocyte quality remains a serious problem for female infertility', said Professor Hiroshi Tamura from the Yamaguchi University Graduate School of Medicine, Japan, who led the research. 'So far no practical and effective treatment for improving oocyte quality has been established'.
High levels of oxidising agents - a type of chemical compound - in the follicular fluids surrounding the egg indicate if a woman has low quality oocytes. These can 'stress' and damage the oocyte. The team took one of these agents known as8-OHdG and measured its levels in follicular fluid samples. Levels of melatonin, which is known to have anti-oxidising effects, were also measured.
The team found that, as melatonin concentration in the follicular fluids naturally increased, the level of 8-OHdG decreased, leading them to believe melatonin was linked to the reduction of the oxidising agents. They confirmed this finding in mice, and discovered that adding melatonin seemed to reduce the damage to the egg caused by the agents.
Next, the group set up a trial with women coming for IVF treatment at the Yamaguchi University Graduate School of Medicine to see if these findings could have real-world effects on IVF. Women who had failed to become pregnant because of poor oocyte quality after one cycle of IVF were split into two groups - 56 women were given three milligrams of melatonin before the next IVF cycle, and 59 just received a standard IVF cycle without melatonin.
The team found that melatonin treatment significantly increased melatonin concentrations in the women's follicles and significantly decreased concentrations of the damaging 8-OhdG. Their results showed 50 per cent of the eggs from women who taken melatonin could be successfully fertilised, as opposed to 22.8 per cent in the control group. When the eggs were transplanted into the womb, 19 per cent (11 out of the total 56) of the women became pregnant, as opposed to 10.2 per cent (six out of total 59) in the control group. The work was published in the Journal of Pineal Research.
'This work needs to be confirmed, but we believe that melatonin treatment is likely to become a significant option for improving oocyte quality in women who cannot become pregnant because of poor oocyte quality', said Professor Tamura. 'Our next step is to analyze exactly how reactive oxygen species harm the oocyte, and how melatonin reduces oxidative stress in the oocyte'.
Professor Russel Reiter from the UT Health Science Center, San Antonio, Texas, who co-authored the paper, agreed. 'it is important that this work be independently confirmed on larger numbers of subjects'. But he added that the findings 'make perfect sense', as melatonin has been shown to protect many different cells and tissues from oxidative damage - the same type of damage known to occur to oocytes.
Wednesday, September 1, 2010
Pair guilty over illegal internet sperm company
Two men have been found guilty of illegally making sperm available over the internet.
Ricky Gage, 49, and Nigel Woodforth, 43, from Reading, operated Fertility 1st which made sperm available from anonymous donors without a licence.
The men had denied three counts of procuring sperm illegally under the Human Fertilisation and Embryology Act.
They were granted conditional bail but the judge warned them she was considering a prison sentence and fine.
The men will be sentenced at Southwark Crown Court on 24 September.
At the start of the trial the pair had argued that their company was simply an information site which acted as an introduction database, meaning they were not procuring or making sperm available.
But jurors heard a list showed 792 deliveries had been made by the company, which helped make the men an estimated income of £250,000 between October 2007 and November 2008.
It is the first time anyone has been prosecuted under the Human Fertilisation and Embryology Act 1990.
Long waiting lists, shortages of sperm and restrictions on who can obtain treatment may be some of the reasons why women have opted to use unlicensed fertility clinics, also the impression that it might be easier to seek treatment online.
But anyone using fresh sperm from an unlicensed clinic is taking a potentially serious risk because they cannot be sure of the quality of the donation or whether it is free of sexually transmitted diseases.
At licensed clinics donors are given a blood test on the day of donation, repeated six months later because HIV can take this long to show up.
Sperm is frozen during this quarantine period and is only made available once the screening has been done and it has been checked for quality.
The men were reported to the Human Fertilisation and Embryology Authority (HFEA) after one of their clients complained about their unprofessional standards.
Melissa Bhalla-Pentley was hoping to have a baby with her partner when she ordered the sperm through the Fertility 1st website set up by Gage and Woodforth.
Ms Bhalla-Pentley paid the men £380 in total and another £150 for courier delivery and the sperm donor's expenses.
However, she contacted the company when a copy of the donor's medical tests was sent to her with his name visible.
Under the HFEA's Act, the firm should have had a licence.
The law was brought in to ensure that both donors and women wanting to conceive had access to information and counselling, and to help protect against the risks of diseases including HIV.
The website run by Gage and Woodforth, which promised women a "life-changing opportunity towards motherhood", boasted of having more than 300 donors nationwide and a 37% success rate.
Clients were allowed to choose the ethnicity, height, hair colour, education and even hobbies of the sperm donor.
Following the verdict, Professor Lisa Jardine, chair of the HFEA, said: "Getting access to fertility services can be difficult and there can be some very strong emotional pressures when trying to start a family.
"But unlicensed internet sites like these are exploiting women.
"This is a victory for those women."
Subscribe to:
Posts (Atom)