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#71
Research / Will a COVID-19 vaccine change...
Last post by mensfe_admin - 2021-02-09 10:56

1 February 2021 - by Professor Frances Flinter
In order to be approved for use in the UK, vaccines must meet the strict standards of safety, quality and effectiveness set out by the independent Medicines and Healthcare products Regulatory Agency. Any COVID-19 vaccine that is approved must go through the same clinical trials and safety checks as all other licensed medicines.

Vaccines that are approved will have been through three phases of clinical trials. In Phase 1 and Phase 2 trials, vaccines are tested on small numbers of volunteers to check they are safe and to determine the optimum dose. In Phase 3 trials they are tested in thousands of people to see how effective they are. The group that receives the vaccine and a control group that receives a placebo (either saline or a different vaccine) are closely monitored for any adverse reactions or side-effects. Safety monitoring continues after a vaccine has been approved for use.

Conventional vaccines contain inactivated versions of whatever pathogen causes the disease, or the proteins on its surface, triggering an immune response in the body that enables it to fight the real infection subsequently.

Two of the COVID-19 vaccines that have recently been approved for use in the UK were developed using a novel technology that uses RNA. RNA vaccines are also being developed for the treatment of cancer. The approved RNA vaccines are made by Pfizer-BioNTech and Moderna: 43,500 people were involved in the Pfizer-BioNTech trial and 30,000 in the Moderna trial. Safety was closely monitored throughout and there were no serious side-effects.

So far, several million people have now been given a COVID-19 vaccine with very few reports of significant side effects, such as allergic reactions.

A posting on Facebook made the following false claim: 'The COVID vaccine is an RNA vaccine. This will actually change your DNA.'

RNA is an acronym for ribonucleic acid, a nucleic acid. RNA is physically different from DNA: DNA contains two intercoiled strands (a double helix), whereas RNA only contains one single strand. RNA also contains two different bases from DNA – its chemical constituents are different.

The main function of RNA is to carry instructions about the amino acid sequences needed to make proteins from the genes (made of DNA) in the cell nucleus to the cytoplasm, where the proteins are assembled on structures called ribosomes. This communication takes place by messenger RNA (mRNA), which translates the sequence of base pairs in the relevant part of the DNA into a corresponding sequence of the amino acids that will join up to form proteins in a process called translation.

RNA vaccines, such as those made by Pfizer-BioNTech and Moderna, contain synthetic mRNA, which codes for a protein specific to the coronavirus's surface. The body uses this mRNA to build its own copies of these proteins to which the immune system then responds by producing antibodies. This gives the immunised person protection if they are exposed to the real virus later – in this case, SARS-CoV-2, the virus which leads to COVID-19.

RNA vaccines are not made with viral particles or inactivated virus, so they are non-infectious. RNA does not integrate itself into the host genome (DNA) and the RNA strand in the vaccine is degraded once the protein has been made. The introduction of mRNA into human cells does not change the DNA of these cells and if these cells replicate, the mRNA would not be incorporated into the new cells' genetic information.

In addition to the advantages of safety, clinical trials show that RNA vaccines generate a reliable immune response and are well-tolerated. Furthermore, RNA vaccines can be produced cheaply and rapidly and can be adjusted easily, if necessary, to accommodate any future significant mutations that may occur in the virus. RNA vaccines are also faster and cheaper to produce than traditional vaccines.

COVID-19 has caused over two million deaths around the world and caused many more people to suffer long term harm to their health, while no-one has died or even experienced a serious adverse event following vaccination. If we are to escape from the terrible pandemic, which has now reached almost every country in the world, it is essential that people have confidence in the safe and effective vaccines that have been developed at such remarkable speed without cutting any corners.

People who spread false rumours raising concerns about their safety are not only being irresponsible, but they also risk endangering the lives of others. We are incredibly lucky that scientists have developed vaccines that are both safe and significantly more effective than older vaccines (for example flu vaccines) and it is imperative that, once they are available, as many people as possible accept them.

The author works in a COVID-19 vaccination centre and has had one dose of the Pfizer BioNTech vaccine.
#72

The COVID Vaccine: A Shot in the Arm for Fertility Treatment?
8 February 2021 - by Dr Ëlo Luik
The rollout of COVID vaccination programmes has brought with it a renewed hope of a return to normality but has also raised questions about the impact of vaccination on fertility treatment and pregnancy.

To help explain and clarify the advice to fertility patients and clinicians, and to fight misinformation spreading online, the Progress Educational Trust (PET) – the charity that publishes BioNew – held an online event.

'The COVID-19 Vaccine: A Shot in the Arm for Fertility Treatment?' was chaired by PET's director Sarah Norcross, and featured speakers outlining the approaches taken by UK, EU and US bodies.

Professor Jason Kasraie, chair of the Association of Reproductive and Clinical Scientists (ARCS), gave the first presentation – an overview of the UK guidance issued by ARCS and the British Fertility Society (BFS). He emphasised that there is no known risk in giving non-live vaccines to pregnant women or those looking to conceive.

ARCS and BFS say there is no need to avoid pregnancy after vaccination, and women who would benefit from the vaccine should receive it without compromising their planned fertility treatment. However, as with any medical treatment, patients should be involved in the decisionmaking process. Pointing out the prevalence of fearmongering misinformation online, Professor Kasraie stressed the importance of being careful about how risk is communicated, when there is currently no cause for fear.

The next speaker, Dr Anna Veiga, coordinator of the European Society of Human Reproduction and Embryology (ESHRE)'s COVID-19 Working Group, explained that ESHRE's relatively cautious position relates to an absence of concrete evidence.

ESHRE has decided not to offer a universal recommendation on whether or not men and women attempting assisted conception should get vaccinated before starting treatment, and instead emphasises the importance of weighing up the factors that are relevant to each individual patient. ESHRE recommends postponing the start of fertility treatment for at least a few days after the vaccine, to allow the immune response to settle.

Regarding vaccination and pregnancy, ESHRE suggests that pregnant women should not be vaccinated unless they are at particularly high risk. ESHRE also suggests that if a woman becomes pregnant after receiving the first vaccine dose then, then – unless the woman is at particularly high risk – the second dose should be delayed until the pregnancy is over. There is no advice to avoid pregnancy after vaccination.

Despite this cautious approach towards the vaccine, Dr Veiga noted that pregnant women have been shown to be at higher risk of developing severe COVID-19 compared to non-pregnant women. Women may therefore still decide to go ahead with vaccination, since the benefits of protection from COVID-19 might outweigh any theoretical risks from, vaccination.

Dr Sigal Klipstein, member of the American Society of Reproductive Medicine (ASRM)'s COVID-19 Task Force, explained that the ASRM's more permissive advice is based on assessing the known and very real risks of COVID-19 alongside the largely theoretical risks of the vaccine. As such, the ASRM recommends vaccination to everyone who can access the vaccine – whether before or during pregnancy – on the grounds that the benefits outweigh the risks.

To emphasise this point, Dr Klipstein gave the example of Israel's decision to make pregnant women a priority group for vaccination, due to their increased risk of developing severe COVID-19. Dr Klipstein further emphasised the important role of fertility specialists in promoting vaccination to their patients, their communities and the public, so as to counter worrying trends of vaccine hesitancy.

During the event, attendees were polled on whether they thought a consensus was needed between all relevant professional bodies on the COVID vaccine and fertility treatment. A clear majority (77 percent) voted yes, prompting Norcross to ask the panel if there was any hope of a consensus being worked out. All three speakers agreed that a uniform message would help avoid confusion and vaccine hesitancy, but that it would be difficult to achieve a consensus, due to each national body's need to follow the formal position of their country's health authorities. The speakers did, however, note that there was significant agreement on key points.

While most of the discussion focused on vaccination of women and the impact on pregnancy, there was an audience question about the impact vaccination might have on sperm quality. The panel agreed that there is no suggestion of risk to the quality of sperm, but that it might be beneficial for men to leave some time between vaccination and fertility treatment, simply to avoid any temporary side effects of the vaccine (such as a fever) having an effect on sperm production. However, it remains prudent for men to get vaccinated before a planned conception, not least so that they avoid the risk of transmitting COVID-19 to the pregnant woman.

Several audience questions addressed the lack of evidence available on the impact of the vaccine. The panel agreed that while there is currently little evidence on the impact of the vaccines on IVF treatment, gamete donation or the health of newborns, there is new information coming in constantly and at unprecedented speeds. Studies of long-term effects will by their nature take time, but there is reassurance to be drawn from studies undertaken on other non-live vaccines.

Dr Klipstein warned against the temptation of an overabundance of caution in the absence of data, as this could end up forcing women into an impossible scenario of weighing up the risk posed by COVID-19 to their own health with any theoretical risks to their baby from the vaccine. Professor Kasraie observed that IVF patients are known to be especially anxious during the pregnancy, so placing them in a position where they have to shield throughout the nine months of pregnancy – for fear of catching COVID-19 – could exacerbate their isolation and anxiety.

Overall, the event showed that despite some differences in the advice given by UK, EU and US bodies, there is significant agreement on the important role of vaccination in protecting the health of fertility patients and professionals alike. Evidence of the harm that can be caused by COVID-19 during pregnancy is clear, known and real. Evidence of harm that can be caused by COVID vaccines is at best theoretical and unsupported by evidence. Certain precautions may be taken in the absence of data, but it is important to ensure that such precautions are not taken to be an indication that there is a known risk.

PET is grateful to the Edwards and Steptoe Research Trust Fund, the British Fertility Society, the Bristol Fertility Clinic and CooperSurgical for supporting this event.
#73
Research / The COVID Vaccine: A Shot in t...
Last post by mensfe_admin - 2021-02-09 10:48

8 February 2021 - by Dr Ëlo Luik
The rollout of COVID vaccination programmes has brought with it a renewed hope of a return to normality but has also raised questions about the impact of vaccination on fertility treatment and pregnancy.

To help explain and clarify the advice to fertility patients and clinicians, and to fight misinformation spreading online, the Progress Educational Trust (PET) – the charity that publishes BioNew – held an online event.

'The COVID-19 Vaccine: A Shot in the Arm for Fertility Treatment?' was chaired by PET's director Sarah Norcross, and featured speakers outlining the approaches taken by UK, EU and US bodies.

Professor Jason Kasraie, chair of the Association of Reproductive and Clinical Scientists (ARCS), gave the first presentation – an overview of the UK guidance issued by ARCS and the British Fertility Society (BFS). He emphasised that there is no known risk in giving non-live vaccines to pregnant women or those looking to conceive.

ARCS and BFS say there is no need to avoid pregnancy after vaccination, and women who would benefit from the vaccine should receive it without compromising their planned fertility treatment. However, as with any medical treatment, patients should be involved in the decisionmaking process. Pointing out the prevalence of fearmongering misinformation online, Professor Kasraie stressed the importance of being careful about how risk is communicated, when there is currently no cause for fear.

The next speaker, Dr Anna Veiga, coordinator of the European Society of Human Reproduction and Embryology (ESHRE)'s COVID-19 Working Group, explained that ESHRE's relatively cautious position relates to an absence of concrete evidence.

ESHRE has decided not to offer a universal recommendation on whether or not men and women attempting assisted conception should get vaccinated before starting treatment, and instead emphasises the importance of weighing up the factors that are relevant to each individual patient. ESHRE recommends postponing the start of fertility treatment for at least a few days after the vaccine, to allow the immune response to settle.

Regarding vaccination and pregnancy, ESHRE suggests that pregnant women should not be vaccinated unless they are at particularly high risk. ESHRE also suggests that if a woman becomes pregnant after receiving the first vaccine dose then, then – unless the woman is at particularly high risk – the second dose should be delayed until the pregnancy is over. There is no advice to avoid pregnancy after vaccination.

Despite this cautious approach towards the vaccine, Dr Veiga noted that pregnant women have been shown to be at higher risk of developing severe COVID-19 compared to non-pregnant women. Women may therefore still decide to go ahead with vaccination, since the benefits of protection from COVID-19 might outweigh any theoretical risks from, vaccination.

Dr Sigal Klipstein, member of the American Society of Reproductive Medicine (ASRM)'s COVID-19 Task Force, explained that the ASRM's more permissive advice is based on assessing the known and very real risks of COVID-19 alongside the largely theoretical risks of the vaccine. As such, the ASRM recommends vaccination to everyone who can access the vaccine – whether before or during pregnancy – on the grounds that the benefits outweigh the risks.

To emphasise this point, Dr Klipstein gave the example of Israel's decision to make pregnant women a priority group for vaccination, due to their increased risk of developing severe COVID-19. Dr Klipstein further emphasised the important role of fertility specialists in promoting vaccination to their patients, their communities and the public, so as to counter worrying trends of vaccine hesitancy.

During the event, attendees were polled on whether they thought a consensus was needed between all relevant professional bodies on the COVID vaccine and fertility treatment. A clear majority (77 percent) voted yes, prompting Norcross to ask the panel if there was any hope of a consensus being worked out. All three speakers agreed that a uniform message would help avoid confusion and vaccine hesitancy, but that it would be difficult to achieve a consensus, due to each national body's need to follow the formal position of their country's health authorities. The speakers did, however, note that there was significant agreement on key points.

While most of the discussion focused on vaccination of women and the impact on pregnancy, there was an audience question about the impact vaccination might have on sperm quality. The panel agreed that there is no suggestion of risk to the quality of sperm, but that it might be beneficial for men to leave some time between vaccination and fertility treatment, simply to avoid any temporary side effects of the vaccine (such as a fever) having an effect on sperm production. However, it remains prudent for men to get vaccinated before a planned conception, not least so that they avoid the risk of transmitting COVID-19 to the pregnant woman.

Several audience questions addressed the lack of evidence available on the impact of the vaccine. The panel agreed that while there is currently little evidence on the impact of the vaccines on IVF treatment, gamete donation or the health of newborns, there is new information coming in constantly and at unprecedented speeds. Studies of long-term effects will by their nature take time, but there is reassurance to be drawn from studies undertaken on other non-live vaccines.

Dr Klipstein warned against the temptation of an overabundance of caution in the absence of data, as this could end up forcing women into an impossible scenario of weighing up the risk posed by COVID-19 to their own health with any theoretical risks to their baby from the vaccine. Professor Kasraie observed that IVF patients are known to be especially anxious during the pregnancy, so placing them in a position where they have to shield throughout the nine months of pregnancy – for fear of catching COVID-19 – could exacerbate their isolation and anxiety.

Overall, the event showed that despite some differences in the advice given by UK, EU and US bodies, there is significant agreement on the important role of vaccination in protecting the health of fertility patients and professionals alike. Evidence of the harm that can be caused by COVID-19 during pregnancy is clear, known and real. Evidence of harm that can be caused by COVID vaccines is at best theoretical and unsupported by evidence. Certain precautions may be taken in the absence of data, but it is important to ensure that such precautions are not taken to be an indication that there is a known risk.

PET is grateful to the Edwards and Steptoe Research Trust Fund, the British Fertility Society, the Bristol Fertility Clinic and CooperSurgical for supporting this event.
#74
About donation

We are given to receive and we will give in return.

We will unconditionally give love to an embryo that we will support in its development for 9 months.

Our child will be born and the amount of love will not disappear, it will grow just like him.

The genetic aspect is transformed by what we wish to give.

The donation will bring us the base like a cake and it's us who will be in charge of the topping, by adding our environment, our love and our philosophy of thinking.


In other words, we are the ones who will create our genes, our family.


We wish you all the best.

Cecile and Seb.
#75
About donation

We are given to receive and we will give in return.

We will unconditionally give love to an embryo that we will support in its development for 9 months.

Our child will be born and the amount of love will not disappear, it will grow just like him.

The genetic aspect is transformed by what we wish to give.

The donation will bring us the base like a cake and it's us who will be in charge of the topping, by adding our environment, our love and our philosophy of thinking.


In other words, we are the ones who will create our genes, our family.


We wish you all the best.
#76
Published 20 October 2020

New guidance from ESHRE for maintaining safe fertility services during a dramatic spike in COVID-19 case numbers has realigned mitigation steps according to local levels of infection.

As countries throughout the world face up to a second wave of COVID-19 infections, ESHRE and others have upgraded safety guidelines for fertility clinics. ESHRE has reaffirmed its guidance from April on the reopening of clinics after lockdowns ('phase 2' of the pandemic), but has now in this latest phase added two further measures as complementary to that April guidance: more testing in addition to the triage questionnaires; and greater information to patients on COVID-19 and its prevention before and during pregnancy.(1)

The new guidance also advises that mitigation measures should be in place depending on the level of infection in a region. Thus, a first core step in this latest guidance is to recognise the current epidemiological status of the pandemic and to assess its likely impact on internal resources (such as staff and equipment) and on patients. The second step is to plan mitigation measures according to that assessment to reduce those risks. A local notification rate of 20 to 60 cases per 100,000 population ('moderate impact') might require no further measures than those already applied routinely. However, an area of 'major' (60-120 cases per 100,000) or 'critical' (>120 cases per 100,000) would require more intensive measures – such as more routine testing of patients and staff, remote consultations, no accompanying persons, routine use of PPE, and even a freeze-all transfer policy. The measures relative to the case notification rate are set out in clear diagrammatic form in the ESHRE guidance.

The guidance was made public just a few days after the ESHRE COVID-19 working group published its review of resuming fertility services with mitigation measures after the initial flare of the pandemic.(2) The paper describes the measures needed to restart safe routine treatments in fertility clinics and the rationale behind their application. The review (published as an 'opinion') covers patient selection and informed consent, staff and patient triage and testing, the modification of ART services, treatment planning and a code of conduct. The code of conduct, as set out in ESHRE's April guidance on the second phase of the pandemic, remains an important component of this latest guidance on the third phase.

The ASRM, though without the same infection spikes in the USA as seen in Europe, has also updated its COVID-19 recommendations to reaffirm the 'judicious' delivery of reproductive care within a framework of careful preventive measures.(3) With COVID-19 case numbers still running high in the USA, the ASRM describes these measures as 'critical in managing this ongoing pandemic'.

The worry for clinics back in Europe must be whether this second wave of infection becomes so critical in some countries that some centres might have to close once again. However, it now seems clear that the guidance on the resumption of routine treatments provided by ESHRE, the ASRM and other authorities has offered effective protocols for the safe provision of service. The paper from the ESHRE COVID-19 working group just published provides strong point-by-point evidence of that.(2) And it's on this basis that the UK's HFEA, for example, on 13 October reassuringly reported that with such professional guidelines in place 'a new national closure of fertility clinics should not be necessary'. However, as ESHRE's latest guidance notes, the HFEA also recognises that staff sickness or patient restrictions may yet force some clinics to close. It's likely that some countries may also requisition hospital beds for intensive care support.

Meanwhile, patients and staff may be further reassured by results from a case report from Spain in which two asymptomatic oocyte donors tested positive for SARS-CoV-2 infection before egg collection.(4) The eggs were subsequently donated for research for the presence of viral RNA. However, total RNA amplification from single cells of their vitrified-warmed oocytes failed to detect the presence of any viral RNA of SARS-CoV-2 in the cells. The authors thus concluded: 'Our report suggests that vertical transmission in these women may not occur through their oocytes during treatment, and that handling of this material in the clinical embryology laboratory may not constitute a hazard for healthcare professionals.'

However, a meta-analysis just published in Nature Communications of 176 published cases of SARS-CoV-2 infections in neonates has found that the majority of them (around 70%) occurred postnatally, although vertical transmission 'may be possible' in around 30% of the cases, either intrapartum or congenital.(6) Some 9% of these latter cases were actually confirmed as vertical infections. Just over half the infected neonates went on to develop COVID-19, while the rest were asymptomatic. One of the investigators, Daniele De Luca from the Antoine Béclère hospital in Paris, said that it was important for doctors to be aware that neonates can be born with the virus or contract it while in hospital. 'At the beginning of the pandemic, some argued that this would never touch babies,' he reported. 'It's rare, but it does exist.' Breastfeeding seemed not associated with SARS-CoV-2 infections, suggesting that viral transmission through the milk, if any, 'should be rare'.

Further details on COVID-19 and pregnancy, including updates from ongoing registry studies, continue to be provided in detail by the UK's RCOG.(5)
#77
26 October 2020 - by Susan Tranfield-Thomas
Egg freezing has been around for 20 years now, originally as an intervention for women who were about to lose their natural fertility through cancer treatment and/or surgery. Somehow it has passed into collective consciousness as an accessible fertility 'fix' and is even on offer to women in the US as part of an employment package. It is now increasingly of interest to thirty-something women who have needed to defer the option of motherhood for other reasons. Some of the media have shaped this into a narrative of 'career women' being 'too busy' to have children but wealthy enough to access egg freezing as a convenient way to control personal biology. This predictably simplistic stereotype ignores the complex reasons why women choose this option.

Billed as a 'forum for civilized disagreement', this hour-long webinar, Egg freezing – what's the deal with fertility preservation?, offers an opportunity to understand what egg freezing is, how and why it is accessed and what its long-term implications are for the women who use it. In addition, its expert contributors offer much-needed insights into recent research, raising useful questions about the continuing marketisation of egg freezing and its ability to deliver what it promises.

Professor Frances Flinter starts the webinar by introducing findings from a report by the Nuffield Council on Bioethics, aimed at public engagement and highlighting a mismatch between the number of people having eggs frozen to those actually defrosted and used. The process, which is invasive and similar to IVF, tends to result in a one in five chance of a viable pregnancy from healthy defrosted eggs. However, a lack of transparency over the data, as well as the targeting of women through the use of algorithms and so-called 'Prosecco parties' may mean that women's anxieties are exploited into buying expensive and ultimately unnecessary procedures.

Dr Kylie Baldwin, a medical sociologist, describes it as a 'numbers game';  a single cycle and egg retrieval – at around £4000 a time, perhaps with one year's storage included – might, optimistically, result in ten eggs, of which five survive the freezing process, and ever-decreasing odds of fertilisation and viable pregnancy. The more eggs, the greater the odds, but this requires a robust bank account, and for a woman in her late thirties, the chances of producing good quality eggs is already dwindling considerably.

In the UK, the average age for freezing eggs is 38, according to Professor Joyce Harper, professor of reproductive science at University College London, so the opportunity to have several cycles and 'bank' the resulting eggs is curtailed quite considerably compared to a woman in her late twenties. Comparing it to IVF, she thinks it should be considered very much a 'plan B'.

We heard from Helen, who defied medical advice to go through a retrieval cycle prior to embarking on treatment for an aggressive, hormonally-driven cancer. Her account of being pressured into daily scans (at £300 a time) on top of a £4000 fee is a reminder of the way commercial interests can abandon pretence at ethical treatment at a time when a patient is at their most vulnerable. Happily, four years after treatment for cancer, Helen has a young daughter (her one remaining embryo) and clearly feels it was all worth it. One can imagine many untold stories with a different ending.

Ultimately, it takes two to make a baby – Tessa Murray, director of communications at Tortoise Media who ran the webinar, challenged us to consider the role of men, their own dwindling sperm count over the last few decades and the continuing focus on women in the drive to 'correct' fertility problems. It would have been useful to explore that issue from first principles, as egg freezing seems to be uniquely the woman's domain, but this was beyond the scope of the webinar.

Claudia Williams, chairing, added her personal perspectives as a 27 year old woman. One hour is hardly enough to do justice to a contentious topic like egg freezing, but the evident expertise of the panel and the generosity of all participants in sharing perspectives from their own lives made this an absorbing experience. For further discussion, it would be useful to engage further with the issues surrounding women in the workplace and working towards swifter change in society.

The workplace should be supporting women with family-friendly policies. It should be eminently possible to return from maternity leave at the same level of seniority. Egg freezing should not be a 'graduation present' to young women, in the expectation they will devote their early working lives in an exclusive relationship with the workplace. The mere idea of 'Prosecco parties' is enough to send shivers down the spine, and not just because it is a ghastly drink designed for teeth-grinding headaches and rampant heartburn; rather, it reinforces a tiresome stereotype of women as prey to impulse and collective neurosis. Whereas the reality tends to be that deciding to freeze one's eggs is a more introspective, considered and intimate process.

I took from this webinar a strong feeling that this thoughtfulness on the part of the women concerned should be at least matched with transparency by the clinics providing this service, over the reality of expectations of success and the cold hard facts of the financial outlay required, which could leave even a relatively well-heeled professional seriously divested of hard-won financial security.

#78
26 October 2020 - by Charlotte Spicer
Scientists have directly delivered proteins to mouse testes for the first time, in an attempt to treat male infertility.

The team of researchers from Seoul National University, South Korea, successfully delivered an important protein, necessary for sperm production, into the testes of infertile mice and restored normal reproductive function.

Infertility affects around 15 percent of couples worldwide, with male infertility thought to be linked to anywhere between 20-70 percent of these cases. Damage to the blood-testis barrier (BTB), which normally protects sperm cells from any harmful substances within the blood, is one cause of reduced sperm production.

Although gene therapy has the potential to correct defects underlying male infertility, there remains a number of safety and ethical concerns. The adverse long-term effects of genome editing of germ cells and risk to future generations remain unknown.

In the current study, published in ACS Nano, the scientists developed an alternative approach, using nanoparticles to directly deliver proteins to the testes. The delivery system, called Fibroplex, consisted of spherical nanoparticles made of silk fibroin, which were coated in lipids.

The Fibroplex was loaded with a protein required for normal function of the BTB, known as PIN1. The entire complex was then injected into the testes of young male mice which had been genetically engineered to lack the PIN1 protein, making them infertile.

The scientists found that Fibroplex safely delivered the PIN1 protein to the mouse testes and did not lead to any toxicity or testicular damage. The treatment increased sperm stem cell numbers and repaired the BTB. In addition, the treated mice had an increased number of mature sperm. Although the sperm count was still only around half of that of normal fertile mice, the treated mice were able to father a similar number of pups, whilst untreated PIN1-deficient mice were unable to reproduce.

The beneficial effects of the treatment lasted for approximately five months, after which the PIN1 protein degraded.

Further studies are now needed in order for scientists to understand whether this approach may be an effective strategy for treating infertility in humans.
#79
26 October 2020 - by Annabel Slater
'Age and fertility – a topic that never gets old.' So said Sarah Norcross - director of the Progress Educational Trust (PET), the charity which publishes BioNews - excusing herself for the pun as she chaired the latest PET event 'Age-Old Question: Exploring Fertility and Ageing'.

The Office of National Statistics still shows the age of conception for men and women is rising. What are the consequences, and what is the understanding of experts and the general public?

The first speaker was Richard Anderson, professor of clinical reproductive science at the University of Edinburgh, who discussed female ageing and fertility at a clinical level. Women create all their eggs before they're born, in the form of immature egg follicles. Throughout their life, even before puberty, the numbers of these follicles decline.

Nonetheless, older women are having babies more than ever, with numbers of mothers in their late 30s having tripled since 1980. Yet the chance of miscarriage increases dramatically with age. According to data from the Human Fertilisation and Embryology Authority (HFEA), the occurrence of live birth following in vitro fertilisation (IVF) is over 30 percent for a woman under 35, and as low as 3-4 percent for a woman in her 40s.

What can be done? Science offers a few options, which Professor Anderson outlined: freeze your eggs, freeze part of your ovary, or use another younger woman's eggs. The first option, egg freezing, continues to increase in popularity and is an area of great research interest. Yet a Spanish study found that out of 5289 women who froze their eggs, only 12.1 percent went on to use them. Data also suggest that only one egg out of 20-25 collected will result in a baby.

Evidence suggests that the reasons women opt for elective egg freezing are due to partner choice, wish for financial stability, and their housing situation, instead of the 'glossy, slightly trite' adverts about egg freezing circulating in the US and probably soon in the UK. Professor Anderson said what is needed is an evidence-based, unbiased information source such as Michelle Peate's Decision Aid. It's essential that women, and men, should recognise the likelihood of success of egg freezing and the associated costs and risks.

Next to speak was Evelyn Telfer, professor of reproductive biology at the University of Edinburgh, and lead researcher at the lab which first created a mature human egg entirely outside the human body (see BioNews 937).

Professor Telfer spoke of a technique for storing pieces of ovary which contain primordial follicles. These immature follicles can be cultured to produce mature eggs, at about a 30 percent success rate – one possible approach to in vitro gametogenesis (IVG). This process is known as a 'multi-step culture system', and has been used to examine the effect of age, chemotherapy, and the role of signalling pathways.

But the big question is whether ovaries have the capacity to make new eggs. Are there germline stem cells in the adult human ovary? This question was answered in 2012 in a Nature Medicine publication showing that this cell type could indeed be isolated from the adult human ovary (see BioNews 646). Professor Telfer's lab has since reported that under the right conditions, such stem cells may be able to form new eggs (see BioNews 872).

Professor Telfer and her team are now investigating eggs produced by IVG, to find how similar they are to conventional eggs. Extensive further research will be needed before any clinical applications are developed.

Christopher Barratt, professor of reproductive medicine at the University of Dundee, delivered a talk focused on male fertility. Ageing somatic tissue can be disguised somewhat – consider those middle-aged celebrities who seem to have looked young for decades. Yet reproductive tissue changes with age, and the effects are visible in studies.

Is the age of first-time fathers increasing? Yes. In Australia in 1976, the average age of new fathers was 27.5 years old. Now, it is 33.5 years.

Is older reproductive age significant? Yes. Studies show that older men have lower odds of conception – a drop of 50 percent for men aged 35-39, compared to under 25-year-olds (see BioNews 974). Older men have increased semen abnormalities, incur a higher risk of premature birth and low birth weight, and other endocrine influences influencing their reproductive success, such as lower libido.

Furthermore, older fathers are also linked to higher rates of autism and schizophrenia in children. An observational study of four centuries of data in four different populations also indicates that children of older fathers have lower reproductive success and reduced longevity.

What can we do? Educate people, advised Professor Barratt, as knowledge about age and male fertility is very poor. According to Professor Barratt, even university science students don't tend to know how age impacts male fertility.

Dr Vasanti Jadva, principal research associate at the University of Cambridge's Centre for Family Research, addressed the psychological impact of older reproductive age on both parents and their children. Studies concerning older parent and child psychology are mixed, she reported. The findings are further confounded by different definitions for older parenthood, a lack of studies examining impact on later childhood, and how large cohort studies can't always identify mechanisms to explain the differences. Older women facing stressful fertility problems may also experience poorer mental health.

Judging by the studies that do exist, children do not appear to be adversely affected by having older parents. If anything, it is the parents themselves who may be adversely affected - some studies of older mothers reported lower social support, worse relationships with their partners, and more parental stress.

Another study indicated that older mothers are more likely to use donor eggs. They may also report regret in not having more children. Dr Jadva concluded that more studies are needed to investigate aspects of older parenthood.

It was time for questions. Professor Barratt was asked if men should be freezing their gametes to avoid age-related issues, as women do. Not likely on a global scale, he said, since sperm freezing is quite costly.

Asked about the production of eggs from ovarian stem cells, Professor Telfer recalled her initial reluctance to believe that she and her colleagues had achieved this. Their achievement continues to rock the scientific community, and is still controversial (see BioNews 1038). The adult stem cells that do exist in the ovarian tissue are not there to make new eggs normally. Professor Telfer stressed that while research using animal models is ongoing, research using human cells is still at an early stage.

What current steps and systems exist to raise awareness about age and fertility? Professor Barrett said it was 'blatantly obvious' that society overall does not understand its reproductive capacity. An unfair burden is placed on women, and that better education needs to implemented, beginning with young people. Dr Jadva agreed that many people don't understand that fertility declines with age, and that fertility studies tend to focus on people who have already started facing difficulties.

An audience member commented that the challenges discussed during the event were not just issues for science and medicine, but for policymakers and society more broadly, and were challenges that faced women and men alike.

#80
mproving choices for fertility patients during a pandemic
27 April 2020 - by Sarah Norcross
So many fertility patients are experiencing the heartbreak of IVF cycles being cancelled, or treatment being halted partway through a cycle, during the global coronavirus/COVID-19 pandemic. For some older patients who may not get another chance, the enforced cessation of treatment is particularly devastating.
Everyone working in the fertility sector recognises that time is of the essence for patients experiencing infertility. It is good to see the UK fertility community working together, through bodies such as the British Fertility Society and the Association of Reproductive and Clinical Scientists, to ensure that processes are in place for a safe and smooth reopening of fertility clinics as soon as this is deemed possible.
As clinics begin to operate once more in countries including Denmark, the Netherlands and Spain, the UK can learn from the experiences in these countries. The European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine are doing valuable work considering whether, when and how treatment might be resumed.
But resuming treatment is only part of the challenge. For people who fall afoul of age-related access criteria imposed by England's Clinical Commissioning Groups (CGCs), there has been no assurance that the clock has stopped ticking. Given the circumstances, the Progress Educational Trust (PET) – the charity that publishes BioNews – has been urging CCGs to effectively 'stop the clock' in relation to accessing NHS-funded fertility treatment, so that patients are not disadvantaged through no fault of their own.
PET understands that this is what will happen in Scotland, where fertility treatment is commissioned centrally. We hope CCGs will follow suit, and thereby help patients who already had to contend with an IVF postcode lottery before the current pandemic added to their difficulties.
We are delighted that our work has prompted the UK Government to stop the clock in one crucial respect – namely, by granting a two-year extension to the ten-year legal limit on storage of eggs, sperm and embryos, as reported elsewhere on BioNews this week. This extension is a pragmatic solution to the current situation, and will come as a huge relief to patients who have yet to use their frozen eggs, sperm or embryos to try for a baby.
However, there remains a broader problem to be resolved. The Government's announcement of an extension was influenced by – and underlines the importance of – PET's ongoing #ExtendTheLimit campaign, which calls for a substantial and permanent extension to the ten-year limit on the storage of eggs for non-medical (social) reasons.
This outdated and unscientific limit means that increasing numbers of women face a stark choice between seeing their frozen eggs destroyed, or becoming a mother before they are ready to do so. Please help PET change this situation by signing and sharing our #ExtendTheLimit petition at www.change.org/extendthelimit (if you can post a comment when you sign, then this is even better!).
PET also encourages everyone to respond online to the UK Government's current public consultation on this issue, before the consultation closes next week (on Tuesday 5 May).
The legal, social and medical issues surrounding egg, sperm and embryo freezing were explored at a PET event earlier this year, and PET has made this discussion more widely accessible in a series of online films. Another development reported on BioNews this week concerns special legal requirements for confidentiality and secrecy that apply to fertility treatment, and this too was explored at a recent PET event that is now available to watch online as a series of films.
Unfortunately holding face-to-face public events is not practical at the moment, which is why some of the PET events that were due to take place in coming weeks have had to be postponed or cancelled. But rest assured that we have plans to start holding some of our events online, and will have some exciting announcements to make about this in the near future.
In the meantime, we could not do any of the work discussed above without your support. We appreciate that times are tough and uncertain for many of you at the moment, but please donate what you can to our appeal.
If you are doing your shopping online, please try visiting Easyfundraising first. More than 4000 shops and websites will donate to us for free when you shop online with them using this service. Sign up to support us at www.easyfundraising.org.uk/causes/pet/
Meanwhile, if you are shopping on Amazon UK and you already have an account with them, the best way to support us is via Amazon Smile. In order to do this, go to https://smile.amazon.co.uk and log in using your usual Amazon account (if you are not logged in automatically). Alternatively, use this link to access the Amazon website before you start shopping, and donate a percentage of what you spend to us (at no extra cost to you).