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Issue 928 (27 November 2017)

 

Welcome to BioNews by email, published by the Progress Educational Trust, providing you with news, comment and reviews on genetics, assisted conception, embryo/stem cell research and related areas.

Visit the BioNews website at www.bionews.org.uk where you can subscribe for free to receive BioNews by email in one of three formats, and search the archive of more than 6,000 articles.

 

 

CONTENTS

Comment

News Digest

Reviews

 


 

The reflex DNA method is an improvement on current antenatal screening in the UK

27 November 2017

By Jonathan Bestwick

Wolfson Institute of Preventive Medicine, Queen Mary University of London

Appeared in BioNews 928

Antenatal screening for Down's, Edwards' and Patau's syndromes with the reflex DNA method was shown in our recent study to have higher screening performance compared with the combined test alone, and compared with the proposed recall DNA method (see BioNews 926). In the reflex DNA method, part of the original blood sample from a woman is stored and a DNA test is automatically triggered by a combined test risk of 1 in 800 or higher – negating the need to recall women for an extra blood test.

Catherine Joynson at the Nuffield Council of Bioethics, in her comment article last week (see BioNews 927) gives unfounded general opinions and ignores the improvement in antenatal screening performance afforded by the reflex DNA method compared with the recall method in which women are recalled for a second screening test (DNA) following an initial positive test (combined test).

The reflex DNA method has a higher detection rate (95 versus 81 percent) and a lower false-positive rate (0.02 versus 2.3 percent) than the recall method.(1) Although most of the false-positives in the recall method are reclassified negative by the DNA test, this does not avoid the distress associated with being recalled on account of a positive screening test. Joynson seems to overlook the substantial advantages of the reflex DNA method.

My response to Joynson's specific comments are as follows:

1. There is no lack of informed choice. Women are informed of what is available and decide on the basis of the screening test regarded as a whole. Obtaining consent for reflex DNA screening is no different from obtaining consent for other established screening tests. The assertion that 'reproductive choice was not given high priority' is incorrect. Joynson raises the question as to whether reflex DNA screening is a test or a method. It is a test as well as a method because the women having the test are given a single test result. In contrast, with the recall method, women are given two test results. Reflex DNA screening was not presented as the invention of a new marker but as the application of a known maker in a way that achieves a more accurate and safer method of screening than existing tests.

2. The accusation that the authors of the reflex project (1) have ignored a 'swathe of research and public debate' with reference to the Nuffield Council report titled 'Non-invasive prenatal testing: ethical issues' (2) is unjustified. The reflex method is only referred to in one paragraph (4.25) of the 169-page Nuffield Council report, which does so incorrectly in a chapter titled 'NIPT in the private sector'. The reflex method was and is provided through the NHS. Policymakers have failed to recognise that the measurement of DNA in screening or diagnosis is not conceptually different from the measurement of proteins, steroids or ultrasound markers. The use of the term NIPT (non-invasive prenatal testing) disguises this fact and fails to recognise that the test is a screening test (not a diagnostic test). The term conceptually isolates the test as non-invasive when all screening tests are non-invasive. NIPT is a term that is best avoided. In practice the question is which of the markers, or combination of markers, achieves the best screening performance at an affordable cost.

3. Joynson argues that the RAPID study (3) using the recall method is better than the combined test alone, as is the reflex method, and implies that the recall method and the reflex method are similar in screening performance. This implication is incorrect as is apparent from the observation that of the 30,790 women screened in the RAPID study there were 118 false-positive results. By comparison in the reflex DNA project there were four false-positive results out of the 22,812 women screened, a rate over 20 times lower. Furthermore the recall screening method leads to women having unnecessary invasive diagnostic tests. In the RAPID study about two-thirds of women who opted for an invasive diagnostic test in the over one in 150 risk category (a category in which they had a choice of a DNA test or a diagnostic test) had an unaffected pregnancy, reflecting the anxiety caused by the initial positive combined test screening result. In the circumstances the women understandably wanted a definitive diagnostic result instead of another screening result.

4. Joynson suggests that an 'extended discussion' (ie counselling) is needed before a woman decides whether to be screened with the reflex DNA test. There is no reason why this process of obtaining consent need be more or less extended than with other tests. Women offered all screening tests are informed of the test in question and choose whether to be screened. They are not counselled at this stage. Counselling is needed once a woman has been identified as having a positive screening result.

5. In connection with the professional duty to 'reduce unnecessary anxiety', Joynson argues that contrary to what is said in our paper nothing is self-evident in this complicated area of medicine. My colleagues and I disagree. Regardless of whether the area of medicine is simple or complicated, causing unnecessary harm is always wrong and unethical.

6. Joynson suggests that reflex DNA screening may not be as good for women with true positive results as it is for those with false-positive results. This is a surprising proposition which has no basis in fact.

7. Joynson raises an issue that does not specifically affect reflex DNA screening, namely that the aim of prenatal screening for Down's syndrome may be to 'screen out' the disorder implying eugenics. There is no way in which an antenatal screening service has anything to do with eugenics. It provides women and their partners with a choice, without pressure to either accept or reject screening. The fact that such screening services are available does not mean that individuals with Down's syndrome are different from other members of society.

I believe that the points made by Joynson are neither correct nor relevant. What is of concern is that she, the Assistant Director of the Nuffield Council on Bioethics, is supporting a poorer method of screening when a better one could be made available at the same or similar cost. I believe that the Nuffield Council should review its position in this area. It should recommend the most effective and safe method of screening for those who consent to screening rather than support an inferior method. It should not recommend obtaining separate consent to individual components of a single screening test.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

20 November 2017 - by Catherine Joynson 
The new 'reflex' method of antenatal screening for Down's, Edwards' and Patau's syndromes was described last week as a 'transformational advance'. It might be cheaper than other approaches, but it could come at the cost of informed choice for pregnant women and couples...
13 November 2017 - by Dr Barbara Kramarz 
A new prenatal screening method for Down's syndrome, Edwards syndrome and Patau syndromes is safer, more reliable and cheaper than existing approaches, a study has found...
18 January 2016 - by Lone Hørlyck 
A new blood test for Down’s syndrome in high-risk women has been recommended for use on the NHS....


 

Shared motherhood IVF for lesbian couples is gaining acceptance in the UK

27 November 2017

By Daniel Bodri, Nick Macklon and Kamal Ahuja

Appeared in BioNews 928

In 2008, parliament voted to scrap the controversial 'need for a father' requirement from the Human Fertilisation and Embryology Act; a consideration for 'supportive parenting' took its place. Alongside legislation giving rights to civil partnership (2004) and to marriage (2014) to same-sex couples, this provided the basis for a sudden surge in fertility treatment options for single and lesbian women. These rights, now given statutory authority in the UK, were echoed in professional treatment guidelines in some, but not all, European countries and the USA. They were reflected too in changing social attitudes. 

The London Women's Clinic's first lesbian couple was treated by donor insemination in 1998. Since then our records indicate that more than 10,000 treatments for patients using donor sperm have been completed at The London Women's Clinic, with good results. One increasingly common request is for a treatment which offers 'shared motherhood' to both partners. The technique allows one partner to provide the egg and the other to provide the uterus for the continuation of pregnancy. Now, in a retrospective analysis of the 121 couples treated between 2011 and 2016, all using donor sperm, we have found high birth rates and reassuringly safe outcomes associated with this method. Results of the study, the first of this kind to be published, will soon appear in the international journal Reproductive BioMedicine Online (Bodri et al. 2018).

The study comprised 121 consecutive lesbian couples whose treatments were mainly performed as fresh embryo transfers, following 141 cycles of IVF and 172 embryo transfers. The cumulative live birth rate per receiver was 60 percent (73 of 121) and the twin delivery rate was 14 percent. The oldest donor achieving a live birth was 40 years old. Live birth rates were slightly higher among those having fresh embryo transfers, although success rates were comparable in all age categories.

The analysis also showed that in 60 percent of couples, no medical cause of infertility was present. Instead, patients chose the treatment to emphasise shared parenthood, to reflect a more positive relationship between the parents and to avoid anonymous egg donation. It's our view that shared motherhood IVF has become increasingly accepted among practitioners and patients, although its overall efficiency and outcomes remain poorly understood. 

With a 60 percent cumulative live birth rate from such a large series (the largest to date by far) we can confirm high levels of efficacy. To minimise the risk of developing the potentially serious complication of OHSS (Ovarian Hyperstimulation Syndrome), clinicians usually used a mild ovarian stimulation treatment.

Over the six-year study period, there was an evident gradual shift to transferring more mature embryos and one rather than two embryos per treatment cycle. In 2011, 25 percent were single embryo transfers. By 2016, 73 percent were single transfers. Overall twin delivery rate was 14 percent. As expected, perinatal outcomes were significantly better for singleton than twin pregnancies, although the latter also had generally favourable outcomes.

It is our view that this approach to shared motherhood IVF for lesbian couples – that is, OHSS-free stimulation with single blastocyst transfer – provides a safe and effective treatment with reassuring obstetric and perinatal outcomes. 

The technique has come a long way since it was first reported in 2010 in a small Spanish study. There it was described as ROPA (receiving eggs/embryos from the partner). Since then, others have described the technique as co-IVF or reciprocal IVF. We favour the term shared motherhood IVF, as this better reflects the emotional connection patients hope to achieve with the child. 

Because of national regulations, shared motherhood IVF is not allowed in France, where fertility patients must have a clear diagnosis of infertility to receive the treatment, Germany and many other countries. However, it is practised in the UK, Spain and Belgium within the regulatory framework. We were therefore not surprised to see overseas couples applying to receive shared motherhood treatment in the UK (Ahuja, 2015). In our study, 12 couples (10 percent) were cross-border patients living in countries where this treatment was not permitted or routinely practised (France: 3, Sweden: 2, Denmark: 1, Norway: 1, Ireland: 1, Bulgaria: 1, Switzerland: 1, Singapore: 1, New Zealand:1). 

The environment in the UK, regulated by the Human Fertilisation and Embryology Act, is clearly welcomed by some patients from other countries who wish to access shared motherhood IVF. In time we feel that shared motherhood IVF will become more widely adopted worldwide. In the meantime, studies on mother-child relationships will become important to understand the psychological wellbeing of children born through this emerging medical procedure.

SOURCES & REFERENCES
Reproductive BioMedicine Online | 27 January 2015
 
Shared Motherhood IVF: High delivery rates in a large series of treatments for lesbian couples using partner-donated eggs (in press)
Reproductive BioMedicine Online | 2018
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

05 December 2016 - by Dr Geeta Nargund 
There has been a 40 percent rise in hospital admissions with severe OHSS in UK fertility clinics in 2015. This extraordinary statistic reveals that the time has now come for firm action to reverse the trend of severe OHSS, a serious but preventable condition...
15 August 2016 - by Ryan Ross 
Three same-sex female couples are suing the US state of New Jersey for what they claim are discriminatory rules regarding the funding of fertility treatment...


 

Gene therapy effective for treatment-resistant leukaemia

27 November 2017

By Sam Sherratt

Appeared in BioNews 928

A new gene therapy for leukaemia is effective for a majority of patients who showed resistance to previous therapies.

The study, published in Nature Medicine, used a new method to treat the most common cancer found in children, pre-B cell acute lymphoblastic leukaemia (B-ALL).

The treatment uses customised immune cells to target a protein present on the surface of B-ALL cancer cells, called CD22. The customised cells, known as Chimeric Antigen Receptor (CAR) T-cells, are created by removing T-cells from a patient's own body, then genetically modifying them to target specific proteins found on the surface of cancer cells. 

The modified T-cells are then re-administered to the patient, causing their immune system attack the cancer more efficiently. Of 15 cancer patients treated in the CD22 study, 11 went into remission.

Previous CAR treatments have involved programming the T-cells to target CD19, a protein often expressed on the surface of leukaemic B-cells. These treatments have proven to be effective in many patients, but in some cases cancer cells do not express CD19 at high enough levels for them to work. 

'The idea that we could have one magic bullet is naïve,' Dr Crystal Mackall, associate director of Stanford University School of Medicine’s Cancer Institute, told the New York Times.

By targeting CD22 instead of CD19, the new therapy induced remission even in five patients who had shown resistance to the anti-CD19 treatment.

However, the results were not all positive. The new therapy induced remission in more than 70 percent of patients, but a significant number eventually relapsed as their cancer cells began to alter their presentation of CD22. 

Researchers hope to overcome this by combining therapies to target multiple proteins at once, rather than just one. Future studies will also need to consider how much of a target is needed for successful, long-lasting treatment, Dr Mackall said. 

'The take-home message is that we've found another CAR T-cell therapy that displays high-level activity in this phase-1 trial,' she said. 'But the relapse rate was also high. So this forces the field to get even more sophisticated.'

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

21 August 2017 - by Emma Laycock 
High doses of vitamin C may help fight certain leukaemias by boosting the activity of a particular gene, suggests a new study...
17 July 2017 - by Dr Loredana Guglielmi 
A drug for leukaemia that genetically alters patients' own cells to fight cancer, has cleared a critical hurdle in gaining commercial approval...
13 June 2016 - by Amina Yonis 
A study on the blood cancer acute myeloid leukaemia has shown which combinations of mutations lead to the most aggressive forms of the disease and revealed a complicated picture at the genetic level...


 

Dolly the cloned sheep did not age prematurely

27 November 2017

By Dr Rachel Huddart

Appeared in BioNews 928

Fears that cloning caused Dolly the Sheep to have early-onset osteoarthritis are 'unfounded', according to new research.

Dolly, the first mammal to be cloned from an adult cell, remains controversial some 21 years after her birth. Her death at the age of almost six, a year after she developed osteoarthritis, was thought to be evidence that cloned animals age prematurely compared with animals conceived naturally. Now, scientists at the Universities of Nottingham, Glasgow and Bristol and the National Museums Scotland in Edinburgh where Dolly's taxidermied body is on display, have shown that cloned sheep, including Dolly, appear to age at the same rate as non-cloned sheep.

After studying sheep cloned from the same cells as Dolly (known as the Nottingham Dollies) and finding that they aged normally in a study published in Nature Communications in 2016, the team wanted to understand why Dolly appeared to have aged differently.

'Our findings of last year appeared to be at odds with original concerns surrounding the nature and extent of osteoarthritis in Dolly – who was perceived to have aged prematurely,' said study author Professor Kevin Sinclair at the University of Nottingham.'Yet no formal, comprehensive assessment of osteoarthritis in Dolly was ever undertaken. We therefore felt it necessary to set the record straight.'

In the latest study, the researchers took X-ray images of the skeletons of Dolly, her naturally conceived daughter Bonnie, and Megan and Morag - two sheep who were born the year before Dolly and were the first animals to be successfully cloned from differentiated cells. Three veterinary surgeons scored each skeleton for the presence and severity of osteoarthritis. The results were compared with those of sheep cloned from the same cells as Dolly, and to those of naturally conceived sheep.

Professor Sandra Corr at the University of Glasgow, a study author, said: 'We found that the prevalence and distribution of radiographic osteoarthritis was similar to that observed in naturally conceived sheep, and our healthy aged cloned sheep. As a result we conclude that the original concerns that cloning had caused early-onset osteoarthritis in Dolly were unfounded.'

The study was published in Scientific Reports.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

16 January 2017 - by Dr Kirsty Horsey 
The third session of the Progress Educational Trust's annual conference featured Professor Sir Ian Wilmut in conversation with Roger Highfield, former Telegraph science editor and now Director of External Affairs for the Science Museum Group...
14 November 2016 - by Jenny Sharpe 
Dolly the sheep was undoubtedly the world's most famous sheep – but how did she come to be, and what did she mean to her creator, Professor Sir Ian Wilmut?...
27 April 2009 - by Dr Rebecca Robey 
In a controversial documentary for the Discovery Channel aired last week, Dr Panayiotis Zavos, a notorious US fertility doctor, claimed to have successfully created and implanted cloned human embryos with the intention of producing live human clones. Scientists and medical ethicists have unanimously condemned him for his...
17 February 2003 - by BioNews 
Dolly the cloned sheep is no more. The Roslin Institute announced last week that she had been put down after a veterinary examination showed that she had a progressive lung disease. Her final resting place will be in Edinburgh - her body is to be preserved for the National Museum of...
31 May 1999 - by BioNews 
Dolly the cloned sheep could be genetically older than her years, according to follow-up research carried out by the Roslin Institute and its commercial arm PPL Therapeutics, where Dolly-style cloning was developed. Dolly may look like a three year old ewe, but the tips of her chromosomes - called telomeres - show...


 

Air pollution linked to poorer sperm quality

27 November 2017

By Dr Rosie Gilchrist

Appeared in BioNews 928

Men living in areas with higher air pollution are also more likely to have a higher proportion of abnormally shaped sperm

Researchers from the Chinese University of Hong Kong analysed sperm quality in samples from more than 6500 Taiwanese men between the ages of 15 and 49. They paired this with satellite imaging data to determine the levels of fine particulate air pollution (PM2.5) around their homes. 

'We found a robust association between exposure to PM2.5 air pollution and low percentage of sperm normal morphology in reproductive-age men,' the scientists wrote in the paper, published in the journal Occupational and Environment Medicine

If there were just 5 micrograms more fine particulates per cubic metre over 2 years around a man's home, there was a 26 percent increased risk of him being in the bottom ten percent of men for normal sperm morphology. The researchers also found an association between increased PM2.5 and higher sperm concentration.

'Although the effect estimates are small and the significance might be negligible in a clinical setting, this is an important public health challenge,' the authors wrote. 'Given the ubiquity of exposure to air pollution, a small effect size of PM2.5 on sperm normal morphology may result in a significant number of couples with infertility.'

The pollution measurements were taken near the men's homes, with a fine resolution of about 1 kilometre. However, many of them would have spent a significant amount of time away from home at work, pointed out Professor Kevin McConway, a statistician at the Open University who was not involved in the study. In addition, although there was an association, this does not prove a causal link. 

Professor McConway also noted that the level of air pollution in cities in Taiwan is generally higher than in cities in the UK.

'If I were young enough to worry about my fertility, I wouldn't put moving to an area with cleaner air at the top of my list of actions – though there are certainly many other health-related reasons to live in cleaner air,' Professor McConway said. 

Professor Allan Pacey, an andrology researcher at the University of Sheffield, added: 'From this and other studies, I remain of the opinion that air pollution probably does have the potential to negatively influence male reproductive health.

'But the jury is still out about quite how and to what extent this impacts on male fertility, rather than measurable and small interesting changes in semen quality.'

SOURCES & REFERENCES
The Independent | 21 November 2017
 
The Telegraph | 21 November 2017
 
Occupational & Environmental Medicine | 21 November 2017
 
The Guardian | 22 November 2017
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

30 October 2017 - by Professor Eric Blyth 
A public event held on 24 October 2017 at the University of Sheffield by the Progress Educational Trust...
23 October 2017 - by Taqdeer Sidhu 
Sleep duration is associated with sperm integrity, according to a recent study in China...
25 September 2017 - by Shaoni Bhattacharya 
Men with obesity are more likely to have a poorer quality and quantity of sperm than men of a healthier weight, suggests a new study...
18 September 2017 - by Dr Kimberley Bryon-Dodd 
A type of chemical found in various personal beauty products and plastics may affect sperm and lower reproductive success, according to a new study...


 

FDA issues warning on DIY gene-therapy kits

27 November 2017

By Theofanis Michailidis

Appeared in BioNews 928

The US Food and Drug Administration (FDA) is taking an active stance against the use of 'do it yourself' gene therapy kits.

'[The] FDA is aware that gene therapy products intended for self-administration and "do it yourself" kits to produce gene therapies for self-administration are being made available to the public,' the agency said in a statement last week. 'The sale of these products is against the law. FDA is concerned about the safety risks involved.'

The warning comes after an incident last month involving biohacker Tristan Roberts, who live streamed injecting himself with an experimental therapy for HIV. Typically the FDA would not intervene in such a case. However, ethical and legal concerns have been raised by experts, particularly over the lack of legislation surrounding self-experimentation.

Eleonore Pauwels, a science policy expert at Wilson Centre in Washington DC, warned about the effects of promoting such actions on social media, highlighting potential risks to vulnerable individuals, such as 'children [or] users with no knowledge or skill' to Gizmodo.

Self-experimentation is not against US law and so cannot be banned, but the FDA can tighten regulation around sale of supplies necessary for self-induced gene therapy, presenting an obstacle to the burgeoning movement of unqualified biohackers who aim to edit the genes of living organisms (including themselves), by ordering the required equipment on the internet.

Gene therapy is the process of inserting working versions of genes into a patient's cells in order to cure or alleviate conditions caused by faulty genes, when no treatment exists. According to the FDA, clinical studies of gene therapy require the submission of an investigational new drug application. Additionally, the marketing of a gene therapy product requires submission and approval of a biologics licence application.

'Consumers are cautioned to make sure that any gene therapy they are considering has either been approved by FDA or is being studied under appropriate regulatory oversight,' the agency said.

SOURCES & REFERENCES
Boston Business Journal | 22 November 2017
 
Wall Street Journal | 22 November 2017
 
FDA | 21 November 2017
 
Gizmodo | 22 November 2017
 
Gizmodo | 18 October 2017
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

20 November 2017 - by Martha Henriques 
The US Food and Drug Administration has announced a fast-track review process for gene therapies and other regenerative medicine treatments...
13 November 2017 - by Jamie Rickman 
The US Food and Drugs Administration has further deregulated direct-to-consumer genetic health risk tests, meaning that some will be approved for market without a pre-market review...
19 October 2017 - by Jennifer Willows 
The US Food and Drug Administration have approved the world’s second gene therapy to target blood cancer...
16 October 2017 - by Rikita Patel 
The US Food Drug and Administration advisory committee has backed the use of gene therapy to treat a hereditary disease for the first time...


 

Human stem cells help paraplegic rats walk again

27 November 2017

By Ewa Zotow

Appeared in BioNews 928

Paraplegic rats were able to walk after being treated with human stem cells. This is the first time lower body movement has been restored after an animal's spinal cord has been completely severed.

After three weeks, sensation returned to the rats' limbs and their spinal cord had started to heal. The use of stem cells may be an effective new method to treat spinal injuries, suggests a study on the findings, published in Frontiers in Neuroscience.

'In the past, scientists have managed to rehabilitate and injured spinal cord using stem cells. But this is the first time that stem cells restored feeling in limbs and complex motor ability, including fast walking, in a significant way, within only a few weeks,' study author Professor Shulamit Levenberg from the Technion-Israel Institute of Technology and Tel Aviv University told Haaretz

The research team used human stem cells from the lining of the mouth and implanted them in a specially designed supporting structure that aided the development and integration of the cells into the rats' nervous system. Three weeks after the treatment, 42 percent of the treated rats showed significant improvement in the ability to walk, balance and support their own weight. Three-quarters had improved sensation in their lower body. 

The treated rats also showed signs of healing in the spinal cord. The connectivity between the brain and the hind limbs was partially restored. None of the control paraplegic rats, which received no treatment, showed any signs of improvement.

Spinal cord injury is one of the leading causes of paralysis and in many cases it is irreversible. Despite substantial progress in the recent years in the treatment of spinal damage, no therapy has been able to restore a completely severed spinal cord. 

However, not all rats benefited from the treatment, with some showing no signs of recovery after receiving the stem cell therapy. Further research is needed to understand the regeneration, and why it worked for some animals and not others. 

The potential of this method for the treatment of people with paraplegia is likely very far off in the future. However, the technique presented here may be a useful starting point in this line of research. 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

11 December 2017 - by Emma Laycock 
An efficient method to collect amniotic fluid rich in stem cells during caesarean sections has been developed by scientists in Sweden...

19 September 2016 - by Dr Greg Ball 
An experimental stem cell therapy appears to have restored some feeling and limb control in five patients paralysed by spinal cord injuries...
25 January 2016 - by Dr Lanay Griessner 
A stem cell treatment routinely used for bone and blood cancers is showing promise at reversing the effects of multiple sclerosis...
26 January 2015 - by Dr Tamara Hirsch 
An early clinical trial investigating a new form of stem cell therapy for multiple sclerosis has demonstrated neurological improvement and enhanced quality of life for patients...
14 July 2014 - by Julianna Photopoulos 
A paraplegic woman in the USA has developed a growth of nasal tissue in her back eight years after failed stem cell therapy...


 

IVF and ICSI linked to congenital heart defects in children

27 November 2017

By Georgia Everett

Appeared in BioNews 928

Children conceived using assisted reproductive techniques (ART) have a greater risk of congenital heart defects (CHDs) compared with children born through spontaneous conception, according to research.

The meta-analysis of eight studies found that the risk of a CHD increased by 44 percent when the child was conceived using IVF  (in vitro fertilisation) or ICSI (intracytoplasmic sperm injection) compared with those conceived without ART.

CHDs were evident in 1.30 percent and 0.68 percent of live births in the ART-conceived group and the spontaneously-conceived group respectively, said the study published in Ultrasound in Obstetrics & Gynaecology.

Dr Paolo Cavoretto, the lead study author, at the IRCCS San Raffaele Hospital in Milan, Italy, said: 'We believe that IVF/ICSI pregnancies present an increased risk of CHDs as a consequence of early placental dysfunction; however, this hypothesis should be demonstrated in future studies.'

He added: 'We recommend fetal echocardiography in all pregnancies from IVF/ICSI.'

The study found that ART did not increase the risk of all cardiac malformations, but only minor CHDs, such as ventricular or atrial septum defects - types of 'holes in the heart'. Dr Katie Morris, a consultant of maternal fetal medicine at the University of Birmingham, noted that the minor CHDs 'would not necessarily be found by a routine scan looking at the baby's heart in detail in the womb'. The research analysed in the study used 'scans to look for heart differences in a variable way, e.g., time, experience of person performing the scan and the detail they looked for'.

She concluded that 'this data, while confirming the increased risk for these pregnancies, does not support a policy in the UK of offering all women conceiving after these techniques a special heart scan (fetal echocardiogram) for their baby', as many minor CHDs would not be detected.

Professor Alastair Sutcliffe, a paediatrician at University College London, suggested that 'the root of all congenital anomalies in ART conception is overbearingly not method, but more why were the couple sub-fertile in the first place'.

The design of the study has also undergone scrutiny. Professor Adam Balen, the chairperson of the British Fertility Society, explained how while the study yielded interesting results, firm conclusions cannot be drawn. 'There could be many reasons for this correlation – for example, people undergoing treatment for infertility are often older – and until all variables can be controlled for, all we can do is say that there might be an association,' he said.

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

24 October 2016 - by Lone Hørlyck 
Bearing a child at a higher age does not increase risk of birth defects when the woman has received IVF or ICSI treatment to become pregnant, a recent study suggests...
19 November 2012 - by Dr Nicola Davis 
Infants conceived by IVF are at significantly greater risk of birth defects compared to naturally conceived babies, announced scientists at a conference last month...
11 June 2012 - by James Brooks 
Use of assisted reproductive technologies like IVF carry with them an increased risk of complications for mother and child, a report from the Royal College of Obstetricians and Gynaecologists highlights...
08 May 2012 - by Dr Rebecca Hill 
The increase in birth defects in babies born after assisted conception could be partly due to underlying fertility problems, according to an Australian study...


 

Illumina wins NIPT patent case in UK High Court

27 November 2017

By Dr Rachel Brown

Appeared in BioNews 928

The UK Patents Court has ruled that two separate non-invasive prenatal tests (NIPT) infringe patents licensed by the US firm Illumina.

Illumina successfully claimed that the Iona test offered by Premaitha Health was in infringement of five patents, and a gender testing component of Ariosa Diagnostics' Harmony test infringed one patent. Unless the judgment is successfully appealed, both tests may be subject to restrictions limiting their sale on the UK market.

Charles Dadswell, Senior Vice President and General Counsel at Illumina has said: 'We are pleased that the court ruled in our favour. The court's judgment validates the investments Illumina has made, the value of this technology and the significant contributions of the inventors in this field.'

Tests such as Iona and Harmony can detect either the gender of the fetus or chromosomal anomalies by assaying fetal cfDNA in the mother's blood. The techniques are therefore considered to be 'non-invasive' forms of prenatal testing, and offer women an alternative to methods such as amniocentesis and CVS that involve sampling cells from the amniotic fluid and placenta respectively, and are associated with increased risk of miscarriage.

NIPT is available on the NHS for pregnancies considered to be at high risk of trisomies (See BioNews 876). Premaitha's contracts to provide Iona to over 50 NHS hospitals could potentially be affected by the ruling.

The court heard claims involving three different patent families licensed by Illumina: Lo 1, Lo 2&3, and Quake 1&2, named for the scientists on whose work they are based (Professor Dennis Lo of the Chinese University of Hong Kong, and Dr Stephen Quake from Stanford University in California respectively). The patents are owned by the universities, except Lo1 which is held by US firm Sequenom, who offer their own NIPT product: MaterniT21. Illumina claimed that it held exclusive licences for all five.

Both Premaitha and Ariosa claimed that the patents under which they are sued are invalid. However, the court ruled in favour of Illumina, stating that all patents are valid and that the tests involved do, at least in some circumstances, infringe upon them. It is expected that the decision will be appealed by the defendants.

Dr Stephen Little, CEO of Premaitha Health, said: 'We are very disappointed with this ruling and deeply disagree with the interpretation the Judge has given to precise technical language in the patents. The effect of the judgment could potentially limit the access of UK patients to NIPT and, in certain respects, diverges from decisions made in other jurisdictions. We are seeking leave to appeal and continue to believe that the motivation behind these legal actions is competitive rather than technical.'

SOURCES & REFERENCES
GenomeWeb | 21 November 2017
 
Business Wire | 21 November 2017
 
British and Irish Legal Information Institute | 21 November 2017
 
Life Sciences Intellectual Property Review | 22 November 2017
 

RELATED ARTICLES FROM THE BIONEWS ARCHIVE

29 February 2016 - by Ryan Ross 
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Event Review: Darwin Lecture: from gene identification to clinical benefit - the example of cystic fibrosis

27 November 2017

By Lea Goetz

Appeared in BioNews 928

The Darwin lecture held at the UK's Royal Society of Medicine (RSM) in London, and jointly organised with the Linnean Society, gives an annual look at topics in science and medicine.

This year's event 'From gene identification to clinical benefit - the example of cystic fibrosis' was delivered by Professor Eric Alton at Imperial College London and the Royal Brompton Hospital, a 'leading authority in this country on cystic fibrosis', according to RSM president Sir Simon Wessely.

Cystic fibrosis (CF) causes more deaths than any other inherited disease in UK, with a median survival of 38 years. Professor Alton explained it as a 'genetic disease of lung water movement'. The disease is caused by a mutation in the CFTR (Cystic fibrosis transmembrane conductance regulator) gene, coding for a protein that spans the cell membrane and transports chloride ions and water from the inside to the outside of cells. With a mutated or missing CF protein, not enough water is transported resulting in a build up of dense mucus, especially in the lungs. In the small airways this leads to the build-up of bacteria, virus and dirt and causes chronic lung infections, which can be fatal.

Professor Alton gave the audience an overview of his work during the past 15 years, aiming to bring gene therapy for cystic fibrosis to the clinic.

The goal is to deliver a normal copy of the CFTR gene into the affected lung cells, which would then be able to produce a functioning protein and could regulate mucus consistency.

In practice, the delivery of therapeutic DNA to the lungs proved extremely difficult. 'We are working against evolution,' Professor Alton told the audience. Natural barriers exist to prevent the transfection of cells with foreign genetic material: the foreign genes have to get into the lung first, then across the thick mucus layer, past the cell membrane and finally into the cell nucleus.

The UK Cystic Fibrosis Gene Therapy Consortium, a team of scientists and clinicians working with Professor Alton, found that an ideal vehicle to pass these barriers would be to co- opt the elaborate intrusion machinery of a virus. Viruses can enter human cells to smuggle their genetic material into the  cell nucleus.

However, the body's adaptive immune system nixed the researchers' plan: because it memorises viruses, they are recognised and discarded on a second infection, which means that therapeutic gene-carrying viruses only work once in a given patient. Instead, the researchers decided to use small lipid drops or liposomes, to pack the CFTR DNA for delivery. While the method is less efficient (lacking the advanced intrusion machinery that viruses have), liposomes can be administered repeatedly, which is necessary to sustain long-term improvement of the CF condition.

Clinical trials have shown that treatment with the liposomes provided a significant effect of 3.7 per cent protection against a decline in lung clearance compared with a placebo (Alton et al, 2015). The consortium have a final product approved and are entering a period of negotiations with pharmaceutical companies.

Professor Alton concluded his lecture by sketching the team's most recent research efforts: it returned to viruses to deliver the CFTR gene more efficiently. However, this time, the researchers managed to circumvent the body's adaptive immune system by combining two types of viruses: a Sendai virus, which provides a specialised ability to transfect lung cells and a lentivirus, which can insert DNA into the lung cell's genome in the long-term. Professor Alton proudly told the audience that the combined virus proved two orders of magnitude more efficiency at transfecting cultures of human cells than the liposomes. Crucially, the scientists demonstrated that - at least in a petri dish - the combined virus can be administered repeatedly, without the cells developing a resistance and that after two years, the transfected cells still produced the CFTR protein. Nevertheless patients would still need repeated treatments, as lung cells are renewed at least every 16 months.

Finally, Professor Alton reflected on what he had learned from the CF gene therapy effort: that gene therapy was about 'delivery, delivery, delivery'. While 'fantastic basic science' had been crucial to the project, the ultimate measure of success was the improvement for the patients. This had only been possible through partnerships between scientists and clinicians.

Following his talk, Professor Alton replied to audience questions, ranging from technical queries about the virus strategy, to political concerns that the Brexit would affect the funding situation for the project. He also explained the stages that gene therapy would have to go through before becoming standard therapy in the NHS: since gene therapy is expensive, treatment through the NHS becomes a question of balancing the benefit to one patient with benefits to other patients.

The final question linked back to Charles Darwin. Given the prevalence of CF, might there be a selective pressure of carrying the CF mutation - such as in the case of sickle cell anaemia, where heterozygous individuals which carry both a mutated and a healthy copy of the gene, are more resistant to malaria infections? Professor Alton explained three current theories: that carrying the CF mutation might confer cholera resistance (because individuals with a defective CFTR and thicker mucus would lose less water during a cholera infection); typhoid resistance (since Salmonella typhi, the bacterium causing typhoid fever, cannot enter cells with a mutated CFTR protein); and finally tuberculosis. Despite these intriguing possibilities, none of the theories fit with current understanding of the mutation's origins and spread  within the human population.

Overall, the lecture was very informative and never lengthy, as Professor Alton didn't miss an opportunity to spice his lecture with jokes and anecdotes, such as declaring a conflict of interest - beard envy to be precise - with lecture's namesake, Charles Darwin. However, the setting was quite formal and the level of the lecture suited an audience with prior medical knowledge not intimidated by the medical habitus and technical terms. The audience was mainly composed of current, future and retired physicians, but I would recommend the lecture to anyone with a serious interest in science and medicine.

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Published by the Progress Educational Trust

CROSSING FRONTIERS

Public Conference
London
8 December 2017

Speakers include

Professor Azim Surani

Professor Magdalena Zernicka-Goetz

Professor Robin Lovell-Badge

Sally Cheshire

Professor Guido Pennings

Katherine Littler

Professor Allan Pacey

Dr Sue Avery

Professor Richard Anderson

Dr Elizabeth Garner

Dr Andy Greenfield

Dr Anna Smajdor

Dr Henry Malter

Vivienne Parry

Dr Helen O'Neill

Dr César Palacios-González

Philippa Taylor

Fiona Fox

Sarah Norcross

Sandy Starr


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