IVF News

The UK Government has announced that the ten-year limit on storing frozen eggs, sperm and embryos will be scrapped.

The current limit of ten years applies to most frozen embryos and gametes and will be replaced by storage periods that can be renewed every ten years up to a maximum of 55 years.

Health minister Sajid Javid said: 'The current storage arrangements can be severely restrictive for those making the important decision about when to start a family, and this new legislation will help turn off the ticking clock in the back of people's minds.'

The current law allows eggs, sperm or embryos belonging to patients who are judged to be 'prematurely infertile' or likely to become so – such as people freezing eggs or sperm prior to cancer treatment – to be kept for up to 55 years. The proposed legislation would do away with this distinction between those who are and are not 'prematurely infertile' and treat all patients equally.

Every ten years patients will be given the choice to continue with storage, or to donate or dispose of their gametes or embryos.

'Technological advances mean that storage of reproductive material is a safe and effective way of protecting fertility for many individuals,' said Dr Raj Mathur, chair of the British Fertility Society. 'This change ensures that UK regulation is compliant with the scientific evidence about the safety of storage, and protects the ability of all our patients to make reproductive choices for themselves as individuals and couples.'

The Progress Educational Trust (PET) – the charity that publishes BioNews – launched its #ExtendTheLimit campaign in 2019, asking Parliament to address the law on egg freezing time limits.

'We are delighted that the Government has seen fit to make the changes we campaigned for,' said PET's director Sarah Norcross. 'Extending the ten-year storage limit on social egg freezing will enable the exercise of reproductive choice, freeing women from the constraints of an outdated, discriminatory and unscientific law, and the threat of having their eggs destroyed against their will or being forced to become a mother before they are ready to do so.'

The change will require new legislation, and so when it becomes law will be dependent on the Parliamentary schedule. However, all patients with frozen gametes or embryos have already been given a two-year extension, due to the disruption to fertility services during the COVID-19 pandemic.

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Researchers have successfully decoded the human embryogenesis process by tracking somatic mutations in adult tissues.  

How a human develops from a single fertilised egg to an adult is a fundamental question in biomedical science. Reconstructing the fate of cells, and the genetic control of this, during early human embryogenesis remains challenging due to limitations on the experiments that can be performed on human embryos. To overcome these limitations, a study published in Nature used whole genome sequencing to identify mutations of 334 single cell colonies and 379 tissues samples taken from seven deceased donors. This analysis produced the world's largest single-cell whole genome sequencing dataset to date. 

'It is an impressive scientific achievement that, within 20 years of the completion of the human genome project, genomic technology has advanced to the extent that we are now able to accurately identify mutations in a single-cell genome. This technology will enable us to track human embryogenesis at even higher resolutions in the future,' said Dr Young Seok Ju from the Korea Advanced Institute of Science and Technology, Daejeon, South Korea and a co-author of the study. 

The research team identified mutations that occur spontaneously in early developmental cell divisions by analysing mutations in adult cells. These early mutations, also called genomic scars, can be used to reconstruct the embryonic development process. The researchers examined the genomic scars of each individual in order to map where each cell in the adult had originated during early embryonic cellular dynamics.

The data revealed that mutation rates are higher in the first cell divisions, but then decrease to approximately one mutation per cell later in life. The whole-genome sequencing analysis showed that our first cells contribute unequally to the development of the embryo and that one cell following the first division of the embryo always leaves more progeny cells than another one. The researchers concluded that three days after fertilisation, cells in the human embryo begin to differentiate into three germ layers and then specific tissues. 

The approach used in the study could be used to improve our understanding of rare diseases caused by abnormalities in embryonic development and thus improve the diagnostics and treatment for these patients.

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Screening for a molecule that inhibits embryo implantation, and timing embryo transfer around this, could improve IVF success rates.

Researchers from RMIT University and Monash IVF in Australia have identified a molecule called podocalyxin (PCX) that makes the lining of the womb resistant to the implantation of the embryo. Levels of this molecule decrease at a certain point during the menstrual cycle, allowing the womb to become 'sticky' and increasing the likelihood of embryo implantation and pregnancy success. Women with low levels of PCX were found to have 53 percent pregnancy success rate following IVF, whereas those with high levels of PCX had an 18 percent pregnancy success rate, the results of a study published in the journal Fertility and Sterility showed.

'We've been looking for something that helps embryos stick when the vital part of the puzzle turned out to be a slippery molecule that has the opposite effect – it prevents them from sticking,' said senior author Professor Guiying Nie of Monash University in Melbourne, Australia.

The team originally identified PCX as an anti-implantation regulator of the embryo in cells isolated from the human endometrial tissue, and announced these results in a paper published in Human Reproduction.

In a subsequent clinical study, the same team examined the levels of PCX in endometrial tissue biopsies collected from 81 patients undergoing IVF. The biopsy of the uterus was performed at the mid-luteal phase (three to five days after ovulation) of the women's menstrual cycle, one full cycle before the transfer of the frozen embryo. The women who had lower levels of PCX detected in their biopsies had a higher pregnancy rate following IVF, than the women who had high levels of the molecule.

A limitation of the finding is that there is no way to screen the endometrial tissue biopsies for PCX levels on the day embryo transfer is due to take place. The research team's future goal is to develop non-invasive and real-time approaches for measuring PCX on the day of embryo transfer. This could eventually be used to optimise timing of embryo transfer to improve IVF success rates, and target PCX levels as a potential cause of infertility.

'We hope with further development our discovery could help clinicians identify precisely when each patient has the greatest chance of achieving pregnancy, delivering fully personalised IVF treatment,' said Professor Nie.

A patent application has been filed for the technology, with the hope future developments could help raise IVF success rates, which currently stand at less than 50 percent.   

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Tuesday 7th September, 2021. 3PM EST/ 8PM GMT / 9PM CET

Moderators:
Dr. Jacques Cohen, Prof. Allan Pacey and Dr. Harry Fisch

Presenters:
"Plastics, Pills and Painkillers: Effects of In-utero Exposures on Male Reproductive Health" Prof. Rod Mitchell
"Sperm Count Decline: The Silent Pandemic?" Prof. Hagai Levine
"Threatened Reproduction: Causes, Consequences and Solutions" Dr. Shanna Swan

View Here

Georg Grieisinger Prof.Dr. Med, MSc will present a recently published article on egg collection in a well-regarded journal with a high impact factor. The presentation will be followed by a live Q&A.

The Maribor consensus: report of an expert meeting on the development of performance indicators for clinical practice in ART
ESHRE Clinic PI Working Group, Vlaisavljevic V, Apter S, Capalbo A, D'Angelo A, Gianaroli L, Griesinger G, Kolibianakis EM, Lainas G, Mardesic T, Motrenko T, Pelkonen S, Romualdi D, Vermeulen N, Tilleman K.
Human Reproduction Open. 2021 Jul 3;2021(3):hoab022. doi: 10.1093/hropen/hoab022. PMID: 34250273; PMCID: PMC8254491.

Note: all participants will get a certificate of participation.

More information and registration on our website.

This webinar introduces attendees to the essentials of egg collection including theoretical principles and best practice based on current data as well as optimization of techniques.

During this webinar Arianna D’Angelo MD will provide participants with the theoretical and practical background necessary to appreciate the critical variables that determine the clinical factors that lead to a successful egg collection.

Note: all participants will get a certificate of participation

More information and registration on our website

BRCA2 mutations may be implicated in infertility, as well as increasing cancer risk, according to new research.

BRCA2 protein complexes work to repair DNA breaks within cells, protecting the integrity of the genome. Mutations in the BRCA2 gene can cause faulty DNA repair mechanisms which in turn confer increased cancer risk (particularly for breast and ovarian cancers). BRCA2 proteins also play a role in the repair of DNA breaks during meiosis, the cell division process by which gametes (eggs and sperm) are made.

'While we have known BRCA2 was necessary for DNA recombination in meiosis, we didn't know how it was able to do this critical job efficiently,' said study author Dr Jayakrishnan Nandakumar, from the University of Michigan.

The process of DNA breaking and repair in meiosis occurs as part of a natural event called crossover, where paired chromosomes are purposely broken, mixed up, and joined back together to 'switch' genes with each other, in order to generate genetic diversity in the gametes. 

In collaboration with the University of Gothenburg in Sweden, the project revealed the structure of a meiosis-specific protein complex involving BRCA2. BRCA2 proteins form a 'sandwich' structure along with proteins called MEILB2, to repair these breaks. 

The researchers found that the 'sandwich' shape of the BRCA2-MEIL2B complex is important to precisely join DNA breakpoints together. DNA repair failures or imprecisions during crossover can lead to genetic defects in the gametes, which may cause infertility.

MEILB2, which is normally only found in cells undergoing meiosis, has also been detected in cancers. The researchers suggest that the aberrant presence of MEILB2 in cancer cells may be preventing normal BRCA2-mediated repair from occurring. 

'The MEILB2 that is part of this repair complex is only supposed to be present in cells that undergo meiosis but MEILB2 has also been found in several cancers. It may be that MEILB2 is very efficiently "hijacking" the BRCA2 in cancer cells, preventing proper repair of the DNA', said Dr Nandakumar.

The study was published in Nature Structural & Molecular Biology.

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The chance of live birth following assisted reproduction is significantly reduced when the prospective father is over the age of 50, a recent study has revealed. 

Despite the belief that male fertility is not subject to a biological clock, a group of researchers at the Centre for Reproductive and Genetic Health in London found that when the father is over the age of 50 the likelihood of a live birth following IVF or ICSI is 33 percent lower than for men under the age of 50. The rates of miscarriage remain unchanged, a finding which is echoed among other similar studies.  

'Paternal age over 50 significantly affects the chance of achieving a live birth following assisted reproductive technology. There should be a public health message for men to not delay fatherhood', the authors wrote.

The findings were originally revealed at the European Society of Human Reproduction and Embryology in 2019, and were published in the journal Acta Obstericia et Gyneologica Scandinavica this month. Data was taken retrospectively from nearly 4300 adults who had undergone IVF or ICSI using fresh sperm and embryo transfer at a single London fertility clinic. This report comes amid a growing trend of men fathering children much later in life. Dr Guy Morris, lead author of the study, said in the Daily Mail that publicised stories of male celebrities over 60 still having children has helped to fuel the incorrect belief that 'male fertility lasts forever'. 

The age-related decline in fertility amongst women is well-documented. Interestingly, the analysis of this data showed that the decline in live births occurred irrespective of female age. This is a particularly important finding as it underlines the previously unknown significance of male age when fathering children. 

This study included males affected by all forms of infertility, thereby improving the validity of these findings, and making them applicable to all couples. Furthermore, the researchers considered additional variables such as semen quality and the method of fertilisation, yet still found that male age negatively impacted fertility independent of the variation in these factors.  

However, several lifestyle factors, including smoking, body mass index and alcohol consumption, could not be controlled. It is plausible that these factors may also negatively influence fertility amongst males. The study did go on to report a lower level of sperm quality amongst males over 50 when compared to those of a younger age. This may begin to explain the decline in fertility, however the mechanisms through which this could occur are yet to be characterised. 

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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. 

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Men who are diagnosed with inflammatory arthritis before the age of 40 are less likely to want children and more likely to be unable to have them. 

According to an observational study in the Netherlands, while men with these diagnoses were more likely to be voluntarily childless, they were also significantly more likely to be involuntarily childless when adjusting for factors including current age, educational attainment, history of cardiovascular disease and partner's fertility, suggesting that inflammatory arthritis or its treatments could impact fertility. Researchers also showed that there was a greater impact on fecundity for men diagnosed before the age of 30, compared to those diagnosed between the ages of 31-40, which is when most fathers have their children in the Netherlands, and there was no impact for men diagnosed after the age of 40. 

'The difference between the desired and final number of children was significantly larger in men diagnosed before and during the reproductive age, indicating that the lower fertility rates are primarily affected by reduced fertility potential and not by a reduced desire for parenthood,' wrote the researchers. Results from the study were published in the British Medical Journal's Annals of the Rheumatic Diseases. 

The team sent out questionnaires to 1841 men between September 2019 and January 2021. They only included men who had completed their families and asked about age at diagnosis, size of desired family, number of children they had and how long it had taken them to conceive, among other questions about their demographic, medical and fertility history. Of the 1841 men sent questionnaires, 628 responded. 

On average, men diagnosed with these conditions prior to their 30th birthdays had 1.32 children, compared with 1.56 for those diagnosed between ages 31 and 40 and 1.88 for those diagnosed when they were age 41 years or older. Furthermore, the percentage of childless men was higher among those diagnosed early. Of those diagnosed before age 30, 34 per cent remained childless compared to between 20-25 percent of all men in the Netherlands. For those diagnosed between age 31 and 40, 27 percent remained childless, and those diagnosed over the age of 40, 17 percent had no children. With further investigation, it was shown that 12 percent of those diagnosed when younger identified as 'involuntarily childless', compared with 10 percent and 4 percent in the two older groups, according to the researchers. 

There are some plausible biological explanations for the associations found, given that reduced sperm production and poor sperm quality are common side effects associated with many of the medications used to treat inflammatory arthritis. Proteins believed to be involved in the development of inflammatory arthritis, including tumour necrosis factor, are also involved in testicular stability and sperm production.

The authors commented that more research was urgently needed to improve the quality of care for men with this diagnosis and their desire for parenthood.

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