Families with genetic diseases support genome-editing research

More than 75 percent of those with a genetic condition, and their family members, support the use of genome-editing technology, a survey has found.

But the survey respondents saw a clear distinction between treating medical conditions and the enhancement of physical or cognitive attributes in healthy people – 86 percent were against using the technology in this way.

The survey was conducted by Genetic Alliance UK and involved 152 respondents who had a genetic condition, or who had a family member with such a condition. The charity’s director, Alastair Kent, said: ‘It is sometimes claimed that advances in genetic technology will result in couples using this new knowledge to “design” babies who will have blue eyes, blond hair, or be good at playing the piano… It should not be forgotten that for couples at risk of passing on a genetic disease the concept of a “designer baby” means nothing more than a baby born free of the genetic threat hanging over their family.’

In January, the Human Fertilisation and Embryology Authority (HFEA) granted the first UK licence to carry out research on human embryos using the CRISPR genome-editing technique (see BioNews 837). And last month the Nuffield Council on Bioethics published its preliminary ethical review of the area (see BioNews 871).

Survey participants were also asked their views about how the technology should be regulated. Nearly all (97.4 percent) felt that there should be regulations in place to control the use of the technology. And the majority favoured a multiple stakeholder approach – involving patients, doctors, scientists and the government – in developing these regulations.

Genome editing offers the potential for treating genetic conditions. ‘There are something like 7000 or 8000 genetic diseases where this is a potential tool for alleviating suffering,’ said Kent. ‘This scientific development is about creating the possibility to make precise alterations in faulty genes, to correct the spelling mistakes that result in dreadful diseases that blight the lives of children. From a parent’s point of view – from a family point of view – if you could make a change that would remove the risk of having a child born with a sentence of premature death hanging over him or her, wouldn’t you want to do it?’

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Online calculator predicts IVF success

An online calculator that can estimate the cumulative success rate of IVF over multiple cycles has been released.

Researchers at the University of Aberdeen developed the tool using national data obtained by the Human Fertilisation and Embryology Authority from over 113,000 women who had undergone IVF or ICSI between 1999 and 2008, using their own eggs and their partner’s sperm.

The calculator is able to estimate a woman’s cumulative chance of a live birth over a course of treatment of up to six cycles of IVF, offering users the opportunity to estimate their chances of having a baby before and after their first cycle of treatment. Based not only on a couple’s circumstances but also treatment information, the tool is able to adjust the initial estimate prior to first treatment for subsequent IVF cycles.

Dr David McLernon, who led the research, said the tool would help ‘keep [patients] better informed and help them prepare emotionally and financially for their treatments’, adding that it could also help clinicians communicate the chance of having a live birth over an entire package of treatment.

Other calculators that are currently available tend to estimate the chance of success after one cycle; the new tool is the first to adjust such an estimate over a number of cycles. It is also able to take into account the use of frozen embryos. The researchers explain that this could help patients prepare for a complete course of treatment since the first cycle does not always succeed.

The new tool is able to take into account certain factors identified by the study that are relevant to a person’s chance of having a baby by IVF, including the woman’s age and duration of infertility, but also factors associated with treatment itself, such as the number of eggs collected, the health of the embryos, their storage and the stage of embryo transfer.

The calculator is not, however, able to take into account all factors that may affect IVF success rates, including the woman’s BMI, ethnicity, smoking and alcohol intake. The researchers also state the calculator should not also be used to decide whether or not couples should have IVF treatment until further research is conducted to examine its effects in clinical practice.

Susan Seenan, chief executive of Fertility Network UK, which was involved in the development of the latest tool, told BBC News that she hoped the calculator would help patients make more informed decisions about their treatment, but stressed that it should not be used in isolation. ‘Anyone considering fertility treatment should discuss their individual chances of success with their clinician,’ she said.

POST-MORTEM INSEMINATION BANNED FOR 40 YEARS

Two administrative justice decisions “have just undermined the bioethics law prohibiting post-mortem procreation using frozen sperm by allowing the latter to be exported

For Jean-Yves Nau, the question is not a new one. It has been asked for the past 40 years, i.e. ever since the freezing of sperm and embryos was first implemented. In the early days of CECOS[1] “a decision was takennot to allow the post-mortem use of sperm preserved by freezing in liquid nitrogen”. The main argument was not to create ‘medically’ assisted orphans. Clinicians followed the opinion of psychiatric experts “who were all extremely hostile to the idea of a child being born with a deceased father. They believed that certain limitations such as death were insurmountable”.

Consequently, “a broad medical and ethical legal consensus was reached to oppose such requests. The ban was set in legal stone with the enactment of the first bioethics laws of 1994″. The debate was not reopened in 2004 orin 2011. Legal actions hit a brick wall. However, the CCNE focused on the issue in 1993 and then again in 2011, expressing “dissent“: “the death of the man should not erase the rights that the woman may consider herself to have over these embryos produced by her and her deceased partner”, it pointed out. Some more cautious members nevertheless believed that “to intentionally contribute to the birth of an orphan, based on the reasoning that the child would be the fruit of a ‘’parental project’’, would revert to the notion that this takes precedence over the interests of the child who should not be deprived of paternal love and education in a situation where the mother’s suffering takes precedence over the suffering of the unborn child”, or even that “the couple’s desire to procreate after death is at risk of being driven by an illusory desire to live on through the child and which would envelop the woman in mourning and her past life”. 

According to the ABM, “the European Union is divided equally between States for and against this practice. Elsewhere in the world, post-mortem MAP (medically assisted procreation) is authorised in South Africa, Australia, Brazil, India, Israel and the United States but banned in South Korea, Hong Kong, Japan, Norway, Singapore and Taiwan”.

 

[1] Centre for the Study and Preservation of Sperm.

Pregnancy later in life may improve cognition in old age

Pregnancy causes many hormonal changes, with some research suggesting it may even impact some of the brain’s functions. A new study suggests there may be cognitive advantages to having a pregnancy later in life.

Pregnancy normally increases the levels of some hormones in the mother’s body, such as estrogen, progesterone, oxytocin, prolactin, cortisol, and some endorphins.

Some studies have linked higher levels of estradiol and cortisol with lower attention and have suggested mothers may have poorer verbal memory during pregnancy.

Negative emotional states have also been reported during pregnancy. In fact, 1 in 9 women experience depression before, during, or after pregnancy, according to the Centers for Disease Control and Prevention (CDC).

However, in the long run, pregnancy hormones may lead to better cognition and memory. A new study investigates the link between age at last pregnancy and a mother’s cognitive abilities later in life.

Assessing the link between reproductive history and cognition

Researchers at the University of Southern California examined the association between reproductive history, hormonal exposure, and cognition in postmenopausal women.

Factors that influence hormonal exposure and that were considered by the study included reproductive period, pregnancy, and use of hormonal contraceptives.

The analysis evaluated a total of 830 women, using data from two clinical trials.

The average age of the participants was 60 years. The researchers made the necessary adjustments for age, race and ethnicity, income, and education.

Participants were evaluated using a variety of cognitive tests and a reproductive history questionnaire. Researchers tested participants’ verbal memory by asking them to remember a list of words or to retell a story after being distracted.

They also assessed their psychomotor speed, attention span, and concentration, as well as their planning abilities, visual perception, and episodic memory.

The findings have been published in the Journal of the American Geriatrics Society.

Pregnancy after 35 linked to better cognition

The study revealed several associations, some of which have been supported by previous research, while others were more surprising.

The study found that postmenopausal women who had their last pregnancy after the age of 35 had better verbal memory.

Those who had their first pregnancy when they were 24 or older had significantly better executive function. This includes attention control, working memory, reasoning, and problem solving.

The study also revealed that having the first menstrual cycle at an early age, along with a longer reproductive life, also led to better executive function in later life.

Estrogen has been shown in previous studies to impact positively on the brain’s chemistry, function, and structure in animal studies, explains lead author Roksana Karim, assistant professor of clinical preventive medicine at University of Southern California’s Keck School of Medicine. Progesterone has been associated with brain growth and development of brain tissue, she adds.

“Starting your period early means you have higher levels of the female sex hormone being produced by the ovaries. Girls are receiving the optimal levels early, so it’s possible that their brain structures are better developed compared to those who are exposed to estrogen levels associated with menstrual cycles at a later age.”

Roksana Karim

Researchers also found that women who had used contraceptives for 10 years or more had better verbal memory and critical thinking skills.

“Oral contraceptives maintain and sustain a stable level of sex hormones in our bloodstream,” Karim says. “Stable is good.”

One result that surprised the researchers was the positive effect an incomplete pregnancy seemed to have on cognitive function.

Women who did not carry their pregnancy to term had better cognition, verbal memory, and executive function, compared with women who had only one full-term pregnancy.

“The finding that even incomplete pregnancies are beneficial was novel and surprising,” says senior author Wendy Mack, professor of preventive medicine at the Keck School of Medicine.

Parity was also found to associate positively with cognition. Women who gave birth to two children had better cognition in older age, compared with mothers of one child.

Results at odds with some previous research

This is the first time a study has investigated the association between age at last pregnancy and cognitive function in older age, Karim says. Having the last baby at a later age can be an indicator of a later surge in pregnancy hormones, the author explains.

“Based on the findings, we would certainly not recommend that women wait until they’re 35 to close their family, but the study provides strong evidence that there is a positive association between later age at last pregnancy and late-life cognition.”

Roksana Karim

However, previous studies have shown that pregnancy can have a negative effect on brain function. Some researchers have found that pregnant women have worse verbal memory and word-listing learning skills, as well as poorer fluency when compared with women who are not pregnant.

Mack explains that such results may have been influenced by other factors, such as other bodily changes or environmental stressors.

“The issue is the human studies have not followed women for the long term. They just looked at women during pregnancy.” she says. “We are not sure if we can expect to detect a positive estrogen effect at that point, as the many bodily changes and psychosocial stressors during pregnancy also can impact women’s cognitive and emotional functions.”

Overall, the new findings are both “intriguing and are supported by other clinical studies and animal studies,” adds Mack.

Men lack knowledge about risk factors contributing to male infertility, study finds

The first large-scale study of its kind has revealed that Canadian men generally lack knowledge about the risk factors contributing to male infertility. Research led by Dr. Phyllis Zelkowitz, head of psychosocial research at the Lady Davis Institute of the Jewish General Hospital, found that men could only identify about 50% of the potential risks and medical conditions that are detrimental to their sperm count and, thus, their prospects to father children. While risk factors such as cancer, smoking, and steroid use were more commonly known, other modifiable risks like obesity, frequent bicycling, and frequent use of a laptop on your lap, were not on their radar.

This study, published in Human Reproduction, highlights the fact that this general lack of knowledge was true for men across all age groups, education and income levels.

“Men aren’t as inclined to ask questions about their health, so it stands to reason that they would be less well informed about their fertility,” explains Dr. Zelkowitz, the Director of Research in the Department of Psychiatry at the JGH and Associate Professor of Psychiatry at McGill University. Nonetheless, about a third of the men surveyed expressed concerns about their fertility, and almost 60% wanted to learn more about this issue.

Most men express the desire for fatherhood at some point in their lives. “Infertility can be devastating for people,” Dr. Zelkowitz says. “When men can’t have children, or have to undertake very expensive treatments, it can have a grave psychological impact. It can lead to depression and put severe stress on relationships.” With rates of infertility having increased in the past 20 years, greater awareness of risk factors and medical conditions associated with infertility can lead to early and preventive interventions to enable men to achieve their reproductive goals.

By shedding light on the issue, the researchers hope to stimulate a dialogue about male fertility and inspire health educators and health care practitioners to provide universal public education to promote reproductive health among men from a young age so that they can take the necessary steps to protect their fertility.

Missouri Appeals Court: Frozen Embryos Property, Not People

A divorced man and woman must mutually consent to using embryos that were frozen and stored while married, a Missouri appellate court has ruled in declaring the embryos marital property, not humans with constitutional rights.

The Missouri Court of Appeals’ 2-1 ruling Tuesday upheld a St. Louis County judge’s 2015 finding that Jalesia “Jasha” McQueen and Justin Gadberry maintain joint custody of the embryos, which have been frozen since 2007. The couple separated in 2010 and divorced last year; dissolution proceedings were drawn out by their dispute over the embryos.

McQueen and her attorney said Wednesday they will appeal, first seeking a rehearing by the appellate court and, if necessary, taking the matter to the Missouri Supreme Court.

McQueen, 44, sued Gadberry because she wanted to use embryos to have more children. But her 34-year-old former spouse doesn’t want to have any more children with McQueen, doesn’t believe he should be required to reproduce and has said through his attorney he would be willing to donate the embryos for research or to an infertile couple or have them destroyed.

The majority ruling, written by Appeals Judge Robert Clayton III, said the court “recognizes the sensitive nature of this case and the differing personal beliefs it evokes — ethical, religious and philosophical — pertaining to scientific advancements in reproductive technology, procreation choice, and the age-old and disputed question of when life begins.

“We are only required to decide whether frozen pre-embryos have the legal status of children under our dissolution of marriage statutes,” Clayton wrote.

He also noted that McQueen’s bid to apply Missouri law defining life as beginning at conception is at odds with U.S. Supreme Court decisions protecting Gadberry’s rights to privacy, freedom from government interference and not to procreate.

Awarding joint custody, Clayton concluded, “subjects neither party to any unwarranted governmental intrusion but leaves the intimate decision of whether to potentially have more children to the parties alone.”

Dissenting Judge James Dowd countered that “Missouri law makes one thing abundantly clear: The two embryos at issue in this case are human beings with protectable interests in life, health and well-being.”

“Further, I disagree with the majority’s presumption that Gadberry’s interests outweigh those of his unborn children,” Dowd added.

McQueen, a lawyer who with Gadberry had twin 9-year-old boys through in vitro fertilization, said the ruling left her “somewhat disgusted.”

It “ignored Missouri statutes that say life begins at conception, and I think that’s a disgrace for the judicial arena and for the people it’s affecting, like me,” she told The Associated Press. “All of the statutes point to one thing — the preservation of life. For them to say otherwise is counter to the point.”

Her attorney, Steve Clark, said the two judges who ruled against McQueen “essentially created law out of thin air” by casting the embryos as property, and “they do not and cannot point to any holding of the U.S Supreme Court that says there’s some sort of right not to procreate.”

Gadberry’s attorney countered that “my client should not be forced to become a parent against his will.” Compelling a frozen embryo to be implanted without consent of both people who created it, Tim Schlesinger added, “subjects private citizens to unwarranted governmental intrusion.”

“What about the people who have six, eight or 10 frozen embryos? Are they required to have six, eight or 10 children?” he said.

In Vitro Fertilisations Babies Born To Women Over 40 May Have Lesser Birth Defects: Study

Babies born to women aged over 40 from assisted reproduction have fewer birth defects compared with those from women who conceive naturally at that age, a new study has found.

This is contrary to widespread belief that the greater risk of birth defects after assisted conception is due to the frequent use of these services by older women.

According to researchers from the University of Adelaide in Australia, this may point to the presence of more favourable biological conditions in IVF (in vitro fertilisations) specific to pregnancies in older women – but they are currently working to determine the exact cause.

The research is based on data of all live births recorded in Australia from 1986-2002, including more than 301,000 naturally conceived births, as well as 2,200 births from IVF and almost 1400 from ICSI (intracytoplasmic sperm injection).

The average prevalence of a birth defect was 5.7 per cent among naturally conceived births, 7.1 per cent for the IVF births, and 9.9 per cent for the ICSI births, across all age groups.

In births from assisted reproduction, the prevalence of birth defects ranged from 11.3 per cent at its highest for women less than age 30 using ICSI, down to 3.6 per cent for women aged 40 and older using IVF.

For natural conceptions, the corresponding prevalence across age groups was 5.6 per cent in young women, increasing to 8.2 per cent in women aged 40 above.

“There is something quite remarkable occurring with women over the age of 40 who use assisted reproduction,” said lead author Michael Davies, professor from University of Adelaide.

“We know from our previous studies that women who undergo assisted reproduction have an increased rate of birth defects compared to women who conceive naturally,” said Davies.

“We also know that among women who conceive naturally, the rate of birth defects increases exponentially from age 35 onwards. Therefore, it was widely assumed, but untested, that maternal age would be a key factor in birth defects from assisted reproduction,” Davies added.

“However, our findings challenge that assertion. They show that infertile women aged 40 and over who used assisted reproduction had less than half the rate of birth defects of fertile women of the same age, while younger women appear to be at an elevated risk,” he said.

“For women treated with IVF and ICSI combined, the greatest age-related risk of birth defects was among the young women, at or around 29 years of age,” he said.

“With a prevalence of 9.4 per cent their risk was more than double the rate of 3.6 per cent observed for the patients aged over 40, and significantly higher than for fertile women of the same age, at 5.6 per cent,” Davies said.

“There is some aspect of IVF treatment in particular that could be helping older women to redress the maternal age issues we see among natural conception, where we observe a transition at around the age of 35 years toward a steadily increasing risk of birth defects,” he said.

The study appears in BJOG: An International Journal of Obstetrics and Gynaecology.

Functional human eggs made from discarded genetic material

US researchers have created functional eggs using DNA from small cells that normally form as waste products during egg development.

The cells, known as polar bodies, bud off eggs during their development and are eventually destroyed. Importantly, they contain identical genetic material to the egg.

‘We know that fertility declines as women get older,’ said Dr Shoukhrat Mitalipov, co-senior author and director of the Oregon Health and Science University Centre for Embryonic Cell and Gene Therapy. ‘This is potentially a way to double the number of eggs we’re able to get from one session of IVF.’

The researchers first collected eggs from 11 women and extracted the DNA from polar bodies. They then created artificial eggs by combining the polar bodies with donor eggs from which the DNA had been removed. After IVF with donor sperm, the artificial eggs went on to develop into embryos.

The team found that only 43 percent of polar body embryos reached the blastocyst stage, compared with 75 percent in the control group. None of the embryos created using polar body DNA were implanted into women so it is not known if they would be capable of producing live, healthy offspring.

Dr Dagan Wells, associate professor at the NIHR Biomedical Research Centre, University of Oxford, who was not involved in the study, acknowledged the work as ‘technically impressive’. He added: ‘It is particularly interesting that the scientists involved were able to use the genetic material from the polar body, a cell which is discarded by the egg as it matures and is traditionally thought of as being little more than a dustbin for the chromosomes that the egg needs to discard in order to make way for those that will be delivered by the sperm.’

This approach could hold promise for women of advanced age who have reduced numbers of eggs, and who may have to undergo more rounds of IVF to become pregnant. Older eggs are also more prone to errors when they are fertilised and begin to divide, so transferring genetic material from older women’s polar bodies into a younger women’s egg could avoid this problem. The technique could also be used to prevent the transmission of mitochondrial diseases.

Although this technique could create more eggs, experts warn that it will not improve their quality. Darren Griffin, Professor of Genetics at the University of Kent cautioned: ‘The oocyte and polar body are genetic reciprocals and this means that if there was a problem with one (e.g. an extra chromosome) we might expect to see a problem (e.g. the same chromosome missing) in the other.’

Kim Kardashian’s Doctors Fear a Third Pregnancy Would Result in Severe Complications

Kim Kardashian West has babies on the brain, but carrying a third child may not be in the cards for the reality star.

On Sunday’s episode of Keeping Up With the Kardashians, Kim revealed that she’s ready to expand her family, but her previous pregnancy complications are making her consider using a surrogate.

During the episode, Kim decided to go talk to her doctor with Kris Jenner about the possible health risks that she would face if she were to have a third child.

“You never know if you might have the same type of problem that could be more serious this time,” Dr. Crane warned her. “You’re always taking a little bit of a chance. There are situations where retained placenta could be life or death.”

“You could bleed to death,” Kris added.

Kim then opted to get a second opinion from fertility specialist. Dr. Wong. He suggested that she really consider using a surrogate, due to the high risks a third pregnancy would create.

“Using a surrogate is not an unreasonable option,” he told Kim. “If our goal is to grow your family like you want to, then a surrogate makes sense.”

“If the two doctors, that I trust, have told me it wouldn’t be safe for me to get pregnant again, I have to listen to that,” Kim revealed during her interview. “But because I don’t know anyone that has been a surrogate or used one, I didn’t really think about that as an option for me.”

Later, the 36-year-old met with a mom who not only carried her own child, but also used a surrogate, in order to pick her brain about the whole experience.

“I’m more worried, because I gave birth to two. There’s a sense in me that because I went through all that pain for these two babies and that I know we did this together…” Kim started to tell Natalie. “There’s no one that would feel your love [like this baby], they are literally near your heart and inside of you.”

“My bond with my kids is so strong,”she continued. “I think my biggest fear is that if I had a surrogate is, would I love them the same? That’s the main thing I keep thinking about.”

Natalie then assured Kim that that’s not  an issue.

“There’s not a day where I have any thought that my love for my kids are different, that my connection to my kids is different,” Natalie told her. “You get to carry one and have them close to you, but then the other is because you so desperately wanted them in your family.”

Towards the end of the episode, Kim decided to discuss the entire surrogate thing with her mom.

“I’ve come to the conclusion in my mind that I can’t carry another one. So now I want to explore surrogacy,” Kim told Kris.

“That scares me for you,” the 60-year-old told her. “What if she gives birth and then grabs the baby and makes a run for it?”

“I don’t think she can,” Kim reassured Kris. “Also, the best thing, I could have a new baby and have no one know and live my life for a good year before we announce it.

“But I don’t know if it’s for me,” she continued. “I really don’t know.”

Missouri Appeals Court: Frozen Embryos Property, Not People

A divorced man and woman must mutually consent to using embryos that were frozen and stored while married, a Missouri appellate court has ruled in declaring the embryos marital property, not humans with constitutional rights.

The Missouri Court of Appeals’ 2-1 ruling Tuesday upheld a St. Louis County judge’s 2015 finding that Jalesia “Jasha” McQueen and Justin Gadberry maintain joint custody of the embryos, which have been frozen since 2007. The couple separated in 2010 and divorced last year; dissolution proceedings were drawn out by their dispute over the embryos.

McQueen and her attorney said Wednesday they will appeal, first seeking a rehearing by the appellate court and, if necessary, taking the matter to the Missouri Supreme Court.

McQueen, 44, sued Gadberry because she wanted to use embryos to have more children. But her 34-year-old former spouse doesn’t want to have any more children with McQueen, doesn’t believe he should be required to reproduce and has said through his attorney he would be willing to donate the embryos for research or to an infertile couple or have them destroyed.

The majority ruling, written by Appeals Judge Robert Clayton III, said the court “recognizes the sensitive nature of this case and the differing personal beliefs it evokes — ethical, religious and philosophical — pertaining to scientific advancements in reproductive technology, procreation choice, and the age-old and disputed question of when life begins.

“We are only required to decide whether frozen pre-embryos have the legal status of children under our dissolution of marriage statutes,” Clayton wrote.

He also noted that McQueen’s bid to apply Missouri law defining life as beginning at conception is at odds with U.S. Supreme Court decisions protecting Gadberry’s rights to privacy, freedom from government interference and not to procreate.

Awarding joint custody, Clayton concluded, “subjects neither party to any unwarranted governmental intrusion but leaves the intimate decision of whether to potentially have more children to the parties alone.”

Dissenting Judge James Dowd countered that “Missouri law makes one thing abundantly clear: The two embryos at issue in this case are human beings with protectable interests in life, health and well-being.”

“Further, I disagree with the majority’s presumption that Gadberry’s interests outweigh those of his unborn children,” Dowd added.

McQueen, a lawyer who with Gadberry had twin 9-year-old boys through in vitro fertilization, said the ruling left her “somewhat disgusted.”

It “ignored Missouri statutes that say life begins at conception, and I think that’s a disgrace for the judicial arena and for the people it’s affecting, like me,” she told The Associated Press. “All of the statutes point to one thing — the preservation of life. For them to say otherwise is counter to the point.”

Her attorney, Steve Clark, said the two judges who ruled against McQueen “essentially created law out of thin air” by casting the embryos as property, and “they do not and cannot point to any holding of the U.S Supreme Court that says there’s some sort of right not to procreate.”

Gadberry’s attorney countered that “my client should not be forced to become a parent against his will.” Compelling a frozen embryo to be implanted without consent of both people who created it, Tim Schlesinger added, “subjects private citizens to unwarranted governmental intrusion.”

“What about the people who have six, eight or 10 frozen embryos? Are they required to have six, eight or 10 children?” he said.