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Started by mensfe_admin - Last post by mensfe_admin
16 August 2021 - by Dr Rachel Montgomery
A recent study has found that as many as one in 15 men carry mutations in their sperm that could impact the health of their children.

Previous research has reported that children born to older men have a higher risk of being born with some conditions, including autism spectrum disorder (ASD). Researchers from the Rady Children's Institute of Genomic Medicine in San Diego, California and the University of California San Diego School of Medicine used whole genome sequencing to determine whether there are any differences in the number of mutations seen in sperm from older men compared with younger men.

'We found that each ejaculate from a man shows an average of 30 mutations,' said co-first author Dr Xiaoxu Yang. 'Almost all of these were found in serial sampling from a period of six to 12 months, whereas most of the mutations were completely absent from a saliva or blood sample.'

Their results, published in Cell, showed that the number of mutations in the semen samples did not, in fact, differ between younger and older men - although the number of mutations in blood samples (reflecting the somatic genome) did increase with age as expected. Further still, the mutations seen were largely unique to the sperm samples, and were not seen in the saliva or blood of the men tested.

Together, this led the researchers to suggest that the mutations seen in the semen samples had not arisen due to age, but instead had been present since birth and had specifically developed in the sperm cells during embryonic development.

Although the mutations were only seen in a small sub-population of the semen samples – a term called clonal mosaicism – the researchers have speculated that they could give rise to diseases in 1 in 300 conceptions.

Senior author Professor Joseph Gleeson said, 'We think that these mutations contribute a substantial burden on human health, potentially causing 15 percent of ASD cases, congenital heart disease and severe paediatric diseases. But we are hopeful that by identifying men at risk, future cases of disease can be avoided.'

The researchers are now working with fertility clinics to assess whether these mosaic mutations are actually passed to embryos, with the goal of ultimately preventing disease in children.

 2 
 :  
Started by mensfe_admin - Last post by mensfe_admin
16 August 2021 - by Dr Rachel Montgomery
A recent study has found that as many as one in 15 men carry mutations in their sperm that could impact the health of their children.

Previous research has reported that children born to older men have a higher risk of being born with some conditions, including autism spectrum disorder (ASD). Researchers from the Rady Children's Institute of Genomic Medicine in San Diego, California and the University of California San Diego School of Medicine used whole genome sequencing to determine whether there are any differences in the number of mutations seen in sperm from older men compared with younger men.

'We found that each ejaculate from a man shows an average of 30 mutations,' said co-first author Dr Xiaoxu Yang. 'Almost all of these were found in serial sampling from a period of six to 12 months, whereas most of the mutations were completely absent from a saliva or blood sample.'

Their results, published in Cell, showed that the number of mutations in the semen samples did not, in fact, differ between younger and older men - although the number of mutations in blood samples (reflecting the somatic genome) did increase with age as expected. Further still, the mutations seen were largely unique to the sperm samples, and were not seen in the saliva or blood of the men tested.

Together, this led the researchers to suggest that the mutations seen in the semen samples had not arisen due to age, but instead had been present since birth and had specifically developed in the sperm cells during embryonic development.

Although the mutations were only seen in a small sub-population of the semen samples – a term called clonal mosaicism – the researchers have speculated that they could give rise to diseases in 1 in 300 conceptions.

Senior author Professor Joseph Gleeson said, 'We think that these mutations contribute a substantial burden on human health, potentially causing 15 percent of ASD cases, congenital heart disease and severe paediatric diseases. But we are hopeful that by identifying men at risk, future cases of disease can be avoided.'

The researchers are now working with fertility clinics to assess whether these mosaic mutations are actually passed to embryos, with the goal of ultimately preventing disease in children.

 3 
 :  
Started by mensfe_admin - Last post by mensfe_admin
2 August 2021 - by Sarah Wood-Heath
Since 1991, the number of IVF cycles has increased significantly with success rates also growing. With freezing techniques improving, according to the Human Fertilisation and Embryology Authority (HFEA), frozen embryo transfers continue to increase year-on-year. In fact, the HFEA state that frozen embryo transfers increased by 86 percent from 2014 to 2019 (see BioNews 1097). According to the HFEA, the typical patient undergoing treatment will have a single fresh embryo transferred in their first cycle with additional embryos stored for use in subsequent cycles.

It is clear that the advancement in such techniques has offered many people the opportunity to have a biological family, who otherwise would not, and embarking on such treatment as a couple is an exciting yet anxious and daunting time. However, storing embryos for future use, means couples run the risk of eventually facing the difficult and often unanticipated question of what should happen to embryos they created together, in the event their relationship breaks down. This is an increasingly challenging area and one which raises extremely sensitive and emotive questions.

At present embryos created for fertility treatment can be stored for a maximum of 10 years under the Human Fertilisation and Embryology Act 1990 (although this has been extended to 12 years due to the COVID-19 pandemic and there are calls to increase it further). A central concept within fertility treatment is that of consent, and whether these frozen embryos, following a separation, can then continue to be stored, used for treatment, or destroyed is dependent on the mutual consent of the parties. By law, the embryos can only be used for the purposes that each of the parties have given their consent to.

At the outset of treatment, the parties' consent is recorded by the completion of various forms with the fertility clinic, however, it is possible for either party to change their mind and subsequently withdraw or vary their consent, in writing, at any point up to the implantation of the embryo in the womb in the UK. This withdrawal or variation can give rise to some difficult and distressing situations.

In the event that one party withdraws their consent to the continued storage of the embryo, then the law requires the fertility clinic to take all reasonable steps to notify those due to be treated with that embryo of the withdrawal. A 12-month cooling-off period is triggered from the date the fertility clinic receives the written withdrawal of consent, during which the embryos will continue to be stored – but cannot be used – to enable the parties to consider their position and the way forward.

After 12 months if both parties do not consent to the continued storage, the embryos will be destroyed. This is a distressing situation for parties following separation where one party is making the difficult decision to destroy the embryos whilst the other wishes to continue to keep them for potential use in the future. This raises such deeply personal and emotional concerns for all involved.

This issue has been challenged through the courts and through to the European Court of Human Rights where the court had to balance one party's wish to use the embryos and the other party's objection to the use of them. The court held that the right to respect for family life did not override the fact that the other party had withdrawn their consent to the embryos being used. The court determined that it has no power to intervene on behalf of the party who wants their embryos to be preserved.

An increasing and not uncommon aspect to the use of embryos is where a separating couple, who remain on amicable terms, are considering moving forwards with using the embryos post-separation. This can raise difficult issues practically, legally, and also emotionally as each party endeavours to understand their role and respective legal positions.  Often, the parties have been on a long journey and despite the separation, they may still wish to support the other in the use of the embryos, whether on a co-parenting basis or one party moving forwards with sole treatment. Consent to one party moving forwards with the use of the embryos solely is often sought on the condition that the other has no legal status or financial responsibility for any child born, and this is a complicated and grey area of the law.

If the parties are married or in a civil partnership and use the embryos in treatment, then both parties will be considered the legal parents unless one party can evidence that they did not consent to the treatment, and this is a complicated legal question. This applies equally whether the second parent is biologically related to the child or whether donor sperm is used. If the parties were not married or civil partners and treatment was with donated sperm or embryos, then in the event of relationship breakdown consideration should be given to any variation or withdrawal of consent to legal parenthood. The law is especially complicated if the embryos were created with the sperm of the former partner and he seeks to donate the embryo to the other party for sole use.

The issues which surround the use of an embryo created in treatment together are wide and far-reaching for the individuals concerned. The strict application of the law can lead to difficult and emotionally challenging situations. The storage and use of the embryos continues to be a matter of mutual consent and in the event of a relationship breakdown, careful consideration needs to be given to the best way forward for both parties involved.

 4 
 :  
Started by mensfe_admin - Last post by mensfe_admin
2 August 2021 - by Sarah Wood-Heath
Since 1991, the number of IVF cycles has increased significantly with success rates also growing. With freezing techniques improving, according to the Human Fertilisation and Embryology Authority (HFEA), frozen embryo transfers continue to increase year-on-year. In fact, the HFEA state that frozen embryo transfers increased by 86 percent from 2014 to 2019 (see BioNews 1097). According to the HFEA, the typical patient undergoing treatment will have a single fresh embryo transferred in their first cycle with additional embryos stored for use in subsequent cycles.

It is clear that the advancement in such techniques has offered many people the opportunity to have a biological family, who otherwise would not, and embarking on such treatment as a couple is an exciting yet anxious and daunting time. However, storing embryos for future use, means couples run the risk of eventually facing the difficult and often unanticipated question of what should happen to embryos they created together, in the event their relationship breaks down. This is an increasingly challenging area and one which raises extremely sensitive and emotive questions.

At present embryos created for fertility treatment can be stored for a maximum of 10 years under the Human Fertilisation and Embryology Act 1990 (although this has been extended to 12 years due to the COVID-19 pandemic and there are calls to increase it further). A central concept within fertility treatment is that of consent, and whether these frozen embryos, following a separation, can then continue to be stored, used for treatment, or destroyed is dependent on the mutual consent of the parties. By law, the embryos can only be used for the purposes that each of the parties have given their consent to.

At the outset of treatment, the parties' consent is recorded by the completion of various forms with the fertility clinic, however, it is possible for either party to change their mind and subsequently withdraw or vary their consent, in writing, at any point up to the implantation of the embryo in the womb in the UK. This withdrawal or variation can give rise to some difficult and distressing situations.

In the event that one party withdraws their consent to the continued storage of the embryo, then the law requires the fertility clinic to take all reasonable steps to notify those due to be treated with that embryo of the withdrawal. A 12-month cooling-off period is triggered from the date the fertility clinic receives the written withdrawal of consent, during which the embryos will continue to be stored – but cannot be used – to enable the parties to consider their position and the way forward.

After 12 months if both parties do not consent to the continued storage, the embryos will be destroyed. This is a distressing situation for parties following separation where one party is making the difficult decision to destroy the embryos whilst the other wishes to continue to keep them for potential use in the future. This raises such deeply personal and emotional concerns for all involved.

This issue has been challenged through the courts and through to the European Court of Human Rights where the court had to balance one party's wish to use the embryos and the other party's objection to the use of them. The court held that the right to respect for family life did not override the fact that the other party had withdrawn their consent to the embryos being used. The court determined that it has no power to intervene on behalf of the party who wants their embryos to be preserved.

An increasing and not uncommon aspect to the use of embryos is where a separating couple, who remain on amicable terms, are considering moving forwards with using the embryos post-separation. This can raise difficult issues practically, legally, and also emotionally as each party endeavours to understand their role and respective legal positions.  Often, the parties have been on a long journey and despite the separation, they may still wish to support the other in the use of the embryos, whether on a co-parenting basis or one party moving forwards with sole treatment. Consent to one party moving forwards with the use of the embryos solely is often sought on the condition that the other has no legal status or financial responsibility for any child born, and this is a complicated and grey area of the law.

If the parties are married or in a civil partnership and use the embryos in treatment, then both parties will be considered the legal parents unless one party can evidence that they did not consent to the treatment, and this is a complicated legal question. This applies equally whether the second parent is biologically related to the child or whether donor sperm is used. If the parties were not married or civil partners and treatment was with donated sperm or embryos, then in the event of relationship breakdown consideration should be given to any variation or withdrawal of consent to legal parenthood. The law is especially complicated if the embryos were created with the sperm of the former partner and he seeks to donate the embryo to the other party for sole use.

The issues which surround the use of an embryo created in treatment together are wide and far-reaching for the individuals concerned. The strict application of the law can lead to difficult and emotionally challenging situations. The storage and use of the embryos continues to be a matter of mutual consent and in the event of a relationship breakdown, careful consideration needs to be given to the best way forward for both parties involved.

 5 
 :  
Started by mensfe_admin - Last post by mensfe_admin
5 July 2021 - by Trine Skuland, Dr Birgit Kvernflaten and Joona Räsänen
It is becoming clear that our gene functions are influenced by a variety of epigenetic factors throughout our lives and even before we are conceived. Environmental context may affect gene expression and which genes are 'activated' or not in children conceived via IVF may be influenced by the dietary and lifestyle habits of an embryo's parents or grandparents, as well as by the culture medium in which eggs and embryos are kept in vitro. These findings have implications for the way we think about fertility, assisted reproduction, and genetic identity.

Epigenetics and bioethics of human embryonic development is a multidisciplinary project that spans disciplinary boundaries in order to better understand how scientists, clinicians, patients, and society should respond to these challenges. The project is funded by the University of Oslo Life Sciences, as part of its convergence environments initiative which has seen interdisciplinary research groups formed to address major health and environmental challenges faced. The project started in 2017, and is now drawing towards its close. Here, three of our project members explain their work within the project.

Trine Skuland is a developmental biologist who works on epigenetic regulation of early embryo development.

When an egg and a sperm unite to form a zygote, numerous events need to be coordinated in order to achieve successful development. Out of the ~30,000 human genes, the right selection has to be switched on/off at the appropriate time point. No wonder these events are error-prone!

Upon fertilisation, extensive reprogramming happens in order to reset the epigenetic marks of the egg and the sperm DNA, and to set up a new pattern that is compatible with further embryo development. Epigenetic marks are chemical groups that are attached either to the DNA itself or to the proteins the DNA wraps around inside the cell nucleus. The pattern of these epigenetic marks will decide whether genes are activated or silenced.

When an embryo reaches the eight-cell stage, one of the most critical events takes place. This is when the first major set of genes is activated. My team is currently studying one specific epigenetic mark that we think is important for the embryonic genome activation and we hope our research will contribute in further characterisation of epigenetic factors involved in this crucial part of embryo development.

Our aim is to find another piece of the big genome activation puzzle in order to get a more complete picture of what is necessary for normal embryo development. This is as more than half of the embryos created during assisted reproduction develop abnormally and have to be discarded. Our ultimate goal is giving infertile people higher quality embryos to increase their chances of becoming parents.

Birgit Kvernflaten is a medical anthropologist who looks at prospective parents' experiences of assisted reproductive technologies. 

My role in the project is to explore prospective parents' experiences and perspectives of practices and treatments used in assisted reproduction. It starts from the idea that their experiences do not take place in a vacuum, but are shaped within a particular socio-cultural and political context. The project further aims to explore and understand prospective parents' experiences and perceptions of the status of the embryo, embryo donation, research, and selection, in light of increased epigenetic knowledge.

This project has highlighted how prospective parents' experiences of infertility treatment are related to and shaped by social and cultural discourses on Norwegian family life.

In Norway, biological or genetic ties are considered central to people's understanding of kinship and identity, shaping couples' negotiations about gamete donation, family, relationships, and responsibilities. Yet people's understanding of genes is also ambiguous. As for the concept of epigenetics; it seems it has not yet entered the public's imagination.

Although the role of environmental factors in shaping who we are is acknowledged in Norwegian society, couples tend to view genetics in a rather deterministic way, in that they believe it shapes both looks, personality, and risk of disease. While difficult to truly grasp, the role of genetics is central to people's ideas about reproduction and parenthood. New epigenetic knowledge raises questions about the interface between nature and nurture, as well as opening up discussion related to the role mothers and their bodies play in determining the health of future offspring.

Joona Räsänen is a bioethicist who works on the philosophical and ethical implications of epigenetics.

Epigenetics raises challenging ethical issues throughout the human life cycle. Epigenetic transmission from one generation to the next may raise questions of moral responsibility of parents and grandparents. Epigenetics plays an important role in a range of chronic diseases, such as diabetes. Our lifestyle habits during pregnancy and even before, may influence whether our future children will live healthy lives or suffer from lifelong illness.

It is commonly known that we should eat healthily for our own sake, but these developments in our understanding of epigenetic could imply that we should eat healthily for the sake of our future children as well. Does this demand too much of future parents?

Epigenetics seems to put prospective parents under pressure since they would be partly responsible for their future child's health even before the child is conceived. Pregnant women are often advised to abstain from alcohol and tobacco, but maybe it is worth reminding them to eat healthily as well – and this advice applies not only to future mothers, but to prospective fathers too, since epigenetic inheritance occurs through the male germline as well.

Conclusion

The interplay between science, anthropology, and philosophy in the context of epigenetics is complex. Skuland notes that a key aim for scientists working to unravel the epigenetic mechanisms involved in early embryo development, is to fulfil the needs of IVF patients to have their 'own' child. Dr Kvernflaten shows how genetics is central to patients' ideas about kinship and identity, yet epigenetics is still something unfamiliar to most prospective parents. Räsänen's example suggests that if parents did take on board some of the moral implications of epigenetics, they might find that the scope of their responsibility for future offspring is dramatically expanded.

Click here to view SOURCES & REFERENCES and RELATED ARTICLES from the BIONEWS ARCHIVE or to leave a comment about this article.

 6 
 :  
Started by mensfe_admin - Last post by mensfe_admin
5 July 2021 - by Trine Skuland, Dr Birgit Kvernflaten and Joona Räsänen
It is becoming clear that our gene functions are influenced by a variety of epigenetic factors throughout our lives and even before we are conceived. Environmental context may affect gene expression and which genes are 'activated' or not in children conceived via IVF may be influenced by the dietary and lifestyle habits of an embryo's parents or grandparents, as well as by the culture medium in which eggs and embryos are kept in vitro. These findings have implications for the way we think about fertility, assisted reproduction, and genetic identity.

Epigenetics and bioethics of human embryonic development is a multidisciplinary project that spans disciplinary boundaries in order to better understand how scientists, clinicians, patients, and society should respond to these challenges. The project is funded by the University of Oslo Life Sciences, as part of its convergence environments initiative which has seen interdisciplinary research groups formed to address major health and environmental challenges faced. The project started in 2017, and is now drawing towards its close. Here, three of our project members explain their work within the project.

Trine Skuland is a developmental biologist who works on epigenetic regulation of early embryo development.

When an egg and a sperm unite to form a zygote, numerous events need to be coordinated in order to achieve successful development. Out of the ~30,000 human genes, the right selection has to be switched on/off at the appropriate time point. No wonder these events are error-prone!

Upon fertilisation, extensive reprogramming happens in order to reset the epigenetic marks of the egg and the sperm DNA, and to set up a new pattern that is compatible with further embryo development. Epigenetic marks are chemical groups that are attached either to the DNA itself or to the proteins the DNA wraps around inside the cell nucleus. The pattern of these epigenetic marks will decide whether genes are activated or silenced.

When an embryo reaches the eight-cell stage, one of the most critical events takes place. This is when the first major set of genes is activated. My team is currently studying one specific epigenetic mark that we think is important for the embryonic genome activation and we hope our research will contribute in further characterisation of epigenetic factors involved in this crucial part of embryo development.

Our aim is to find another piece of the big genome activation puzzle in order to get a more complete picture of what is necessary for normal embryo development. This is as more than half of the embryos created during assisted reproduction develop abnormally and have to be discarded. Our ultimate goal is giving infertile people higher quality embryos to increase their chances of becoming parents.

Birgit Kvernflaten is a medical anthropologist who looks at prospective parents' experiences of assisted reproductive technologies. 

My role in the project is to explore prospective parents' experiences and perspectives of practices and treatments used in assisted reproduction. It starts from the idea that their experiences do not take place in a vacuum, but are shaped within a particular socio-cultural and political context. The project further aims to explore and understand prospective parents' experiences and perceptions of the status of the embryo, embryo donation, research, and selection, in light of increased epigenetic knowledge.

This project has highlighted how prospective parents' experiences of infertility treatment are related to and shaped by social and cultural discourses on Norwegian family life.

In Norway, biological or genetic ties are considered central to people's understanding of kinship and identity, shaping couples' negotiations about gamete donation, family, relationships, and responsibilities. Yet people's understanding of genes is also ambiguous. As for the concept of epigenetics; it seems it has not yet entered the public's imagination.

Although the role of environmental factors in shaping who we are is acknowledged in Norwegian society, couples tend to view genetics in a rather deterministic way, in that they believe it shapes both looks, personality, and risk of disease. While difficult to truly grasp, the role of genetics is central to people's ideas about reproduction and parenthood. New epigenetic knowledge raises questions about the interface between nature and nurture, as well as opening up discussion related to the role mothers and their bodies play in determining the health of future offspring.

Joona Räsänen is a bioethicist who works on the philosophical and ethical implications of epigenetics.

Epigenetics raises challenging ethical issues throughout the human life cycle. Epigenetic transmission from one generation to the next may raise questions of moral responsibility of parents and grandparents. Epigenetics plays an important role in a range of chronic diseases, such as diabetes. Our lifestyle habits during pregnancy and even before, may influence whether our future children will live healthy lives or suffer from lifelong illness.

It is commonly known that we should eat healthily for our own sake, but these developments in our understanding of epigenetic could imply that we should eat healthily for the sake of our future children as well. Does this demand too much of future parents?

Epigenetics seems to put prospective parents under pressure since they would be partly responsible for their future child's health even before the child is conceived. Pregnant women are often advised to abstain from alcohol and tobacco, but maybe it is worth reminding them to eat healthily as well – and this advice applies not only to future mothers, but to prospective fathers too, since epigenetic inheritance occurs through the male germline as well.

Conclusion

The interplay between science, anthropology, and philosophy in the context of epigenetics is complex. Skuland notes that a key aim for scientists working to unravel the epigenetic mechanisms involved in early embryo development, is to fulfil the needs of IVF patients to have their 'own' child. Dr Kvernflaten shows how genetics is central to patients' ideas about kinship and identity, yet epigenetics is still something unfamiliar to most prospective parents. Räsänen's example suggests that if parents did take on board some of the moral implications of epigenetics, they might find that the scope of their responsibility for future offspring is dramatically expanded.

Click here to view SOURCES & REFERENCES and RELATED ARTICLES from the BIONEWS ARCHIVE or to leave a comment about this article.

 7 
 :  
Started by mensfe_admin - Last post by mensfe_admin

21 June 2021 - by Dr Helen Robertson
Female infertility gets a great deal of airtime. From posters on the tube, to dramatic headlines with declarations of 'fertility falling off a cliff at 35 years of age', it's very clear that most of the public awareness around infertility focuses on women.

But this is only telling half the story. A historic lack of investment in targeted treatments means that male infertility hasn't received the attention necessary to raise awareness, open up the conversation, or provide therapeutic options that focus on the cause. More recent media have aimed to break the stigma associated with male infertility: a documentary hosted by comedian Rhod Gilbert (see BioNews 1083) and interviews with Love Island star Chris Hughes (see BioNews 1072) have begun to shed light on a previously neglected topic, but the lack of therapeutic options remains a challenge for individuals and couples facing fertility issues.

With this in mind, last week's online event 'What's in the Pipeline for Male Infertility' provided some much-needed insight into ongoing research into the causes and possible treatments for male fertility issues. The event was produced by the Progress Educational Trust (PET), the charity that publishes BioNews, and was supported by the Scottish Government. It was chaired by PET's director Sarah Norcross and featured speakers from the UK and USA, each working on different aspects of the male infertility story.

Norcross opened the event by providing some context on what current treatment looks like for male infertility. I was surprised to learn that the only regularly offered treatment option for male infertility is ICSI (intracytoplasmic sperm injection), which involves injecting sperm directly into an egg prior to normal IVF embryo transfer. However, ICSI is not a guaranteed route to pregnancy despite being offered as a 'catch-all' for many underlying causes of male infertility. So, what can we do to investigate and treat instances of male infertility, without requiring women to undergo a very invasive treatment that might not result in a successful pregnancy?

First to speak was Dr Sarah Martins Da Silva, senior lecturer in systems medicine at the University of Dundee. Dr Martins Da Silva, who was recently interviewed by Norcross for BioNews (see BioNews 1098), began her talk by explaining the underlying causes of male infertility, and how current therapeutic options (namely ICSI) fall short of providing a reliable solution. She then moved on to discuss the work she is currently involved with, investigating the importance of a protein called phospholipase C zeta (PLC zeta) in egg activation. Work by Dr Martins Da Silva and her team has found that sperm that are deficient in PLC zeta are linked to some instances of male infertility, likely due to a failure of egg activation at the point of fertilisation. By tackling this underlying issue, Dr Martins Da Silva has found that combining ICSI with an assisted egg activation technique – in instances where sperm is found to be low in PLC zeta – can result in improved fertilisation and successful pregnancy outcomes compared to ICSI alone. Focusing on PLC zeta might not be a universal solution, but the work presented by Dr Martins Da Silva shows it has a role as a therapeutic target when investigating male infertility in the future.

Next was Jamie Chorlton, head of clinical development for St George Street Capital, a charity that accelerates clinical trials for drugs with the potential to help patients with unmet needs. One of their current focuses is idiopathic male infertility (IMI) - cases of infertility in men which result from an unexplained reduction in sperm quality. As Chorlton explained, 80 percent of IMI cases have indicators of oxidative stress in semen. By reducing the activity of a pro-oxidant enzyme called myeloperoxidase (MPO), the levels of reactive oxygen species in sperm decreases, which in turn increases sperm quality and can lead to improved fertility. It is hoped that upcoming trials arranged over a three-year period by St George Street Capital will show if taking an MPO inhibitor can improve sperm quality and fertility. If successful, this preliminary work will see the drug licensed back to the original developer for further trials, with the potential for clinical application in instances of male infertility in the future.

The final two talks covered two areas of male infertility that have historically not been a priority: diagnosing male fertility from sperm samples, and pre-emptively treating male infertility as a result of cancer treatment in young men. Dr Tiffany Wood, founder and CEO of Dyneval, spoke about a tool she has developed based on complex fluid properties and how this can aid in sperm diagnosis. Methods for assessing semen have not improved for many years and rely on a slow, manual process. Previous forays into computer-aided semen analysis have been quite hit-or-miss, given their reliance on high concentrations of semen samples. As Dr Wood explained, Dyneval technology has already been successfully applied in agriculture settings and animal reproduction. By working with human fertility scientists (including Dr Martins Da Silva), it is hoped that Dyneval might also be used to assess sperm quality and health in a clinical setting too.

Lastly, Professor Robert Brannigan, from the Department of Urology at Northwestern University, Feinberg School of Medicine, Illinois, spoke about the importance of developing and applying methods that might aid male fertility after cancer treatment. This was something that I had previously read about for young female cancer patients, but it was the first time I had heard about such measures being used to preserve fertility in men. Professor Brannigan explained that although the cryopreservation of sperm is an existing approach, cryopreserving testicular tissue prior to cancer treatment is an emerging technology with the potential to aid fertility in pre-pubescent patients.

Overall, it was interesting to see infertility being explored from a new perspective, and encouraging that many different approaches are being taken to understand the problem in a clinical setting.

Norcross then invited the audience to ask the put questions to the panellists. Many questions came from people looking for treatment options for male infertility, which emphasised how important the work being undertaken in this area is, and how it can impact upon lives on a personal level. As research progresses and the conversation about male infertility opens up, there are exciting prospects for improved treatments and earlier intervention.

 8 
 :  
Started by mensfe_admin - Last post by mensfe_admin

21 June 2021 - by Dr Helen Robertson
Female infertility gets a great deal of airtime. From posters on the tube, to dramatic headlines with declarations of 'fertility falling off a cliff at 35 years of age', it's very clear that most of the public awareness around infertility focuses on women.

But this is only telling half the story. A historic lack of investment in targeted treatments means that male infertility hasn't received the attention necessary to raise awareness, open up the conversation, or provide therapeutic options that focus on the cause. More recent media have aimed to break the stigma associated with male infertility: a documentary hosted by comedian Rhod Gilbert (see BioNews 1083) and interviews with Love Island star Chris Hughes (see BioNews 1072) have begun to shed light on a previously neglected topic, but the lack of therapeutic options remains a challenge for individuals and couples facing fertility issues.

With this in mind, last week's online event 'What's in the Pipeline for Male Infertility' provided some much-needed insight into ongoing research into the causes and possible treatments for male fertility issues. The event was produced by the Progress Educational Trust (PET), the charity that publishes BioNews, and was supported by the Scottish Government. It was chaired by PET's director Sarah Norcross and featured speakers from the UK and USA, each working on different aspects of the male infertility story.

Norcross opened the event by providing some context on what current treatment looks like for male infertility. I was surprised to learn that the only regularly offered treatment option for male infertility is ICSI (intracytoplasmic sperm injection), which involves injecting sperm directly into an egg prior to normal IVF embryo transfer. However, ICSI is not a guaranteed route to pregnancy despite being offered as a 'catch-all' for many underlying causes of male infertility. So, what can we do to investigate and treat instances of male infertility, without requiring women to undergo a very invasive treatment that might not result in a successful pregnancy?

First to speak was Dr Sarah Martins Da Silva, senior lecturer in systems medicine at the University of Dundee. Dr Martins Da Silva, who was recently interviewed by Norcross for BioNews (see BioNews 1098), began her talk by explaining the underlying causes of male infertility, and how current therapeutic options (namely ICSI) fall short of providing a reliable solution. She then moved on to discuss the work she is currently involved with, investigating the importance of a protein called phospholipase C zeta (PLC zeta) in egg activation. Work by Dr Martins Da Silva and her team has found that sperm that are deficient in PLC zeta are linked to some instances of male infertility, likely due to a failure of egg activation at the point of fertilisation. By tackling this underlying issue, Dr Martins Da Silva has found that combining ICSI with an assisted egg activation technique – in instances where sperm is found to be low in PLC zeta – can result in improved fertilisation and successful pregnancy outcomes compared to ICSI alone. Focusing on PLC zeta might not be a universal solution, but the work presented by Dr Martins Da Silva shows it has a role as a therapeutic target when investigating male infertility in the future.

Next was Jamie Chorlton, head of clinical development for St George Street Capital, a charity that accelerates clinical trials for drugs with the potential to help patients with unmet needs. One of their current focuses is idiopathic male infertility (IMI) - cases of infertility in men which result from an unexplained reduction in sperm quality. As Chorlton explained, 80 percent of IMI cases have indicators of oxidative stress in semen. By reducing the activity of a pro-oxidant enzyme called myeloperoxidase (MPO), the levels of reactive oxygen species in sperm decreases, which in turn increases sperm quality and can lead to improved fertility. It is hoped that upcoming trials arranged over a three-year period by St George Street Capital will show if taking an MPO inhibitor can improve sperm quality and fertility. If successful, this preliminary work will see the drug licensed back to the original developer for further trials, with the potential for clinical application in instances of male infertility in the future.

The final two talks covered two areas of male infertility that have historically not been a priority: diagnosing male fertility from sperm samples, and pre-emptively treating male infertility as a result of cancer treatment in young men. Dr Tiffany Wood, founder and CEO of Dyneval, spoke about a tool she has developed based on complex fluid properties and how this can aid in sperm diagnosis. Methods for assessing semen have not improved for many years and rely on a slow, manual process. Previous forays into computer-aided semen analysis have been quite hit-or-miss, given their reliance on high concentrations of semen samples. As Dr Wood explained, Dyneval technology has already been successfully applied in agriculture settings and animal reproduction. By working with human fertility scientists (including Dr Martins Da Silva), it is hoped that Dyneval might also be used to assess sperm quality and health in a clinical setting too.

Lastly, Professor Robert Brannigan, from the Department of Urology at Northwestern University, Feinberg School of Medicine, Illinois, spoke about the importance of developing and applying methods that might aid male fertility after cancer treatment. This was something that I had previously read about for young female cancer patients, but it was the first time I had heard about such measures being used to preserve fertility in men. Professor Brannigan explained that although the cryopreservation of sperm is an existing approach, cryopreserving testicular tissue prior to cancer treatment is an emerging technology with the potential to aid fertility in pre-pubescent patients.

Overall, it was interesting to see infertility being explored from a new perspective, and encouraging that many different approaches are being taken to understand the problem in a clinical setting.

Norcross then invited the audience to ask the put questions to the panellists. Many questions came from people looking for treatment options for male infertility, which emphasised how important the work being undertaken in this area is, and how it can impact upon lives on a personal level. As research progresses and the conversation about male infertility opens up, there are exciting prospects for improved treatments and earlier intervention.

 9 
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Started by mensfe_admin - Last post by mensfe_admin

14 June 2021 - by Dr Kamal Ahuja and Professor Nick Macklon
Among the highlights of the Human Fertilisation and Embryology Authority's (HFEA) latest report on trends in fertility treatment is a continuing upturn in the number of egg donation cycles performed in the UK. In the past 20 years the use of donor eggs with donor sperm has increased 50-fold –  from 27 cycles in 1991 to 1375 cycles in 2019 – while donor eggs with partner sperm increased 22-fold – to 3058 cycles in 2019. Altogether, in 2019, 4433 egg donation cycles were completed in the UK.

The HFEA attributes this increase to the wider use of egg donation in women of an older maternal age, noting a live birth rate of over 30 percent in all patients irrespective of age. Only 17 percent of patients aged 40 and over used donor eggs in 2019, but their use did nevertheless increase with age: eight percent among those aged 40-42, 21 percent for ages 43- 44 and 57 percent for ages 45-50. This trend is one we already see in the USA as reported by the United States Centres for Disease Control and Prevention, where over 12 percent (25,321 out of 196,454 cycles) of all treatment cycles are egg donation, usually in older patients.

The period covered by the report would also have found many UK women having egg donation in overseas clinics, in a pattern of cross-border care already analysed in studies from the European Society of Human Reproduction and Embryology. In addition, we had evidence as published in the journal Human Reproduction that during this period donor eggs and sperm were being sent across borders and between countries, as well as patients travelling to different countries for fertility treatment. However, in 2020 with the outbreak of the COVID-19 pandemic in March, many of these overseas clinics – in Spain, Ukraine, USA and Cyprus – would have been out of bounds to most egg donation patients from the UK, and still off limits in 2021. Based on these restrictions and observations of our own practice at the London Egg Bank, we think it can be stated with some confidence that the UK's primary source of donor eggs is no longer overseas clinics. Egg donation has come home.

Even factoring in the restrictions of the pandemic, this represents a seismic shift and one we forecasted in 2020 in the journal Reproductive Biomedicine Online. We wrote that using frozen eggs 'will quickly become the default standard practice in egg donation' in contrast to the previous use of 'fresh eggs' taken from women participating in IVF egg collections as egg sharers or donors related to patients. We further added that there will be no need for overseas travel, no need to wait for a suitable donor to become available at overseas clinics or for synchronised cycles. A greater choice of donors, and a more efficient programme at a lower cost will be available within the UK. The basis of this forecast was the development of vitrification technology and the ability it has conferred to frozen eggs to retain the same viability as fresh once warmed.

Our more recent publication in the journal Reproductive Biomedicine Online of an analysis of almost 500 egg freezing cycles and subsequent transfers in 705 recipients in a group of patients at the London Egg Bank demonstrates the extent to which vitrification is revolutionising egg donation in the UK and how domestic sourcing of donor eggs can now meet the demands and expectations of recipient patients.

The large group of altruistic donors in this study represents wholly UK sourced donor eggs recruited between January 2017 and December 2019 in a programme introduced to prospective donors and recipients via seminars, the London Egg Bank website and social media. The overall live birth rate per transfer among the 559 recipients matched to donors was 37.9 percent, which varied according to identified predictive factors in the donors (age and ovarian reserve). Estimates of cumulative live birth rates after three embryo transfers exceeded 60 percent. However, recipient age was not a significant predictor of outcome. Singletons were born in 95.5 percent of gestations.

This study not only demonstrates the excellent viability of frozen donor eggs in this series, but also reaffirms the potential to provide enough donor eggs to meet demand in the UK derived only from domestic altruistic donors and recipients turning to a local clinic for treatment. Concurring with the trend for older women to use donor eggs seen in the HFEA report, recipients in this study had a median age of 44 years, with age and low ovarian reserve the most common reasons for seeking treatment. Two-thirds of them had frozen embryos left in storage after treatment.

These results compare well with other studies, although one study from Spain in a large group of egg donation patients sought to compare outcomes from frozen and fresh donor eggs, while another from the USA involved predominantly the transfer of multiple embryos. Our study, over a period of three years, involved a consecutive group of treatments that involved only frozen-thawed eggs, and with a single embryo transfer rate of 87 percent.

While some predictive factors (mainly relating to the donor) do have an influence on outcome, the results of this study should be reassuring to patients that a UK-based domestic egg donation programme can achieve excellent results comparable with those of other cryobanks across the world. The restrictions of the COVID-19 pandemic may well have frustrated most cross-border initiatives in the past year or so, but frozen egg banking can flourish here in the UK, and is now in a prime position to meet the patient demands implicit in the HFEA's latest review.

 10 
 :  
Started by mensfe_admin - Last post by mensfe_admin

14 June 2021 - by Dr Kamal Ahuja and Professor Nick Macklon
Among the highlights of the Human Fertilisation and Embryology Authority's (HFEA) latest report on trends in fertility treatment is a continuing upturn in the number of egg donation cycles performed in the UK. In the past 20 years the use of donor eggs with donor sperm has increased 50-fold –  from 27 cycles in 1991 to 1375 cycles in 2019 – while donor eggs with partner sperm increased 22-fold – to 3058 cycles in 2019. Altogether, in 2019, 4433 egg donation cycles were completed in the UK.

The HFEA attributes this increase to the wider use of egg donation in women of an older maternal age, noting a live birth rate of over 30 percent in all patients irrespective of age. Only 17 percent of patients aged 40 and over used donor eggs in 2019, but their use did nevertheless increase with age: eight percent among those aged 40-42, 21 percent for ages 43- 44 and 57 percent for ages 45-50. This trend is one we already see in the USA as reported by the United States Centres for Disease Control and Prevention, where over 12 percent (25,321 out of 196,454 cycles) of all treatment cycles are egg donation, usually in older patients.

The period covered by the report would also have found many UK women having egg donation in overseas clinics, in a pattern of cross-border care already analysed in studies from the European Society of Human Reproduction and Embryology. In addition, we had evidence as published in the journal Human Reproduction that during this period donor eggs and sperm were being sent across borders and between countries, as well as patients travelling to different countries for fertility treatment. However, in 2020 with the outbreak of the COVID-19 pandemic in March, many of these overseas clinics – in Spain, Ukraine, USA and Cyprus – would have been out of bounds to most egg donation patients from the UK, and still off limits in 2021. Based on these restrictions and observations of our own practice at the London Egg Bank, we think it can be stated with some confidence that the UK's primary source of donor eggs is no longer overseas clinics. Egg donation has come home.

Even factoring in the restrictions of the pandemic, this represents a seismic shift and one we forecasted in 2020 in the journal Reproductive Biomedicine Online. We wrote that using frozen eggs 'will quickly become the default standard practice in egg donation' in contrast to the previous use of 'fresh eggs' taken from women participating in IVF egg collections as egg sharers or donors related to patients. We further added that there will be no need for overseas travel, no need to wait for a suitable donor to become available at overseas clinics or for synchronised cycles. A greater choice of donors, and a more efficient programme at a lower cost will be available within the UK. The basis of this forecast was the development of vitrification technology and the ability it has conferred to frozen eggs to retain the same viability as fresh once warmed.

Our more recent publication in the journal Reproductive Biomedicine Online of an analysis of almost 500 egg freezing cycles and subsequent transfers in 705 recipients in a group of patients at the London Egg Bank demonstrates the extent to which vitrification is revolutionising egg donation in the UK and how domestic sourcing of donor eggs can now meet the demands and expectations of recipient patients.

The large group of altruistic donors in this study represents wholly UK sourced donor eggs recruited between January 2017 and December 2019 in a programme introduced to prospective donors and recipients via seminars, the London Egg Bank website and social media. The overall live birth rate per transfer among the 559 recipients matched to donors was 37.9 percent, which varied according to identified predictive factors in the donors (age and ovarian reserve). Estimates of cumulative live birth rates after three embryo transfers exceeded 60 percent. However, recipient age was not a significant predictor of outcome. Singletons were born in 95.5 percent of gestations.

This study not only demonstrates the excellent viability of frozen donor eggs in this series, but also reaffirms the potential to provide enough donor eggs to meet demand in the UK derived only from domestic altruistic donors and recipients turning to a local clinic for treatment. Concurring with the trend for older women to use donor eggs seen in the HFEA report, recipients in this study had a median age of 44 years, with age and low ovarian reserve the most common reasons for seeking treatment. Two-thirds of them had frozen embryos left in storage after treatment.

These results compare well with other studies, although one study from Spain in a large group of egg donation patients sought to compare outcomes from frozen and fresh donor eggs, while another from the USA involved predominantly the transfer of multiple embryos. Our study, over a period of three years, involved a consecutive group of treatments that involved only frozen-thawed eggs, and with a single embryo transfer rate of 87 percent.

While some predictive factors (mainly relating to the donor) do have an influence on outcome, the results of this study should be reassuring to patients that a UK-based domestic egg donation programme can achieve excellent results comparable with those of other cryobanks across the world. The restrictions of the COVID-19 pandemic may well have frustrated most cross-border initiatives in the past year or so, but frozen egg banking can flourish here in the UK, and is now in a prime position to meet the patient demands implicit in the HFEA's latest review.

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