IVF News

A recent study found that adults conceived through fertility treatment may have a better quality of life in adulthood than those who were naturally conceived. 

Research has already investigated the health of IVF-conceived children, but data about adults is limited because IVF was first implemented relatively recently, in 1978.

'Our findings suggest that being ART [assisted reproductive technology]-conceived can provide some advantages on quality of life in adulthood, independent of other psychosocial factors,' said Dr Karin Hammarberg, lead author of the study at Monash University, Melbourne, Australia.

The study looked at a group of 193 adults conceived through fertility treatment and 86 naturally conceived adults at two separate time points: when they were between 18 and 28 years old and then again between the ages of 22 and 35. 

The study also showed that regardless of their method of conception, adults who were in a better psychological and home environment at the first time point, were more likely to have higher quality of life at the second. 

'Perhaps unsurprisingly, we also found that, independently of how the person was conceived, having a better relationship with parents, less psychological distress, and a better family financial situation in young adulthood contributed to a better adult quality of life,' Dr Hammarberg added.

The psychological wellbeing of the two groups at both time points was assessed using the World Health Organisation Quality of Life – Brief Assessment (WHOQoL-BREF). It is based around four aspects of wellbeing. Physical, which concerns pain, sleep and energy levels; psychosocial, which includes questions on feelings, memory and learning; social relationships, on social support and relationships; and a fourth on their surrounding environment.

Statistical tests showed that adults conceived through fertility treatment had significantly higher scores in the social relationships and environment sections of the test at the second time point.

The researchers speculated that the positive results for children conceived through fertility treatment could reflect the fact that their parents may have a particularly strong desire for a commitment to parenthood.

The two groups also completed a Kessler Psychological Distress questionnaire and an interview about psychological wellbeing at the first time point. The latter included questions around sexual orientation, financial situation, perceptions of their own weight, family relationships, friendships and exercise.

The study was published in the journal Human Fertility. 

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A new study claims to have mapped the genomes of embryos created by IVF, and suggests that the same techniques used could also be used to enable preimplantation genetic testing (PGT).

The paper, published in Nature Medicine, outlines molecular and statistical techniques for inferring the whole genome sequence of three- and five-day-old in vitro embryos using tiny amounts of genetic material. The authors believe that this makes it possible to forecast the risk of developing common diseases, such as cancer and diabetes, that are affected by many different genes. Such an approach to understanding the combined effects of many genes is called a polygenic risk score (PRS).

'Our approach enabled the prediction of both rare and common variants in embryo genomes' wrote the authors, from genomics company MyOme in California. 'Our findings may inform the discussion of utility and implementation of genome-based PGT in clinical practice.'

To construct the genomes of more than 100 embryos, the researchers analysed hundreds of thousands of specific sites across the genome, in a process called genotyping. They filled in the gaps in the genomes with genetic sequences from the prospective parents, and compared their predicted genome to that of the born child.

The authors found that they were able, with 97-99 percent accuracy, to infer the correct sequence at sites used to calculate PRSs for 12 medical conditions. They say that this could enable the creation of PRSs for embryos.

While the method for assembling the genomes of embryos is of interest to the scientific community, the predictive value and ethical implications of so-called 'PGT-P' (PGT that involves PGSs) are controversial. Alongside the paper, Nature Medicine published commentaries pointing to the many scientific and ethical problems with PGT-P, while a similarly critical editorial on the matter was published in Nature proper.

'It is important to stress that this study does not shed light on the most important aspect of using PRSs for embryo selection from IVF, where there are fundamental questions of both the statistical validity of the PRS in this setting and also the ethical appropriateness of procedure', said Professor Ewan Birney, deputy director of the European Molecular Biology Laboratory, who was not involved in the study.

In the UK, selecting an embryo based on the genes it carries is only permitted for couples who are at risk of having a child with a serious genetic condition, such as Huntington's disease or cystic fibrosis. The Human Fertilisation and Embryology Authority has recently stated that it would not be legal to use PGT-P for embryo selection in the UK.

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Bed rest following embryo transfer during IVF has been linked with reduced pregnancy success.

In a meta-analysis of 188 randomised control trials, containing more than 59,000 participants, researchers across the UK analysed the safety and scientific validity of clinical interventions which aim to improve embryo transfer success rates. Across six of these trials, the implementation of bed rest, defined as more than 20 minutes rest following embryo transfer, reduced clinical pregnancy rates by 15 percent. These data provide support for guidelines issued by the American Society for Reproductive Medicine, which discourage this practice.

'This is the first study to present a comprehensive overview of all interventions offered to couples undergoing IVF to help us decide what is the best practice when performing an embryo transfer.' said lead author Dr Bassel Al Wattar from the UCL Institute for Women's Health and UCLH Reproductive Medicine Unit.

During IVF, the fertilised egg is transferred into the womb, with many 'add-ons' offered to assist endometrial receptivity or to encourage implantation, often despite empirical evidence. In addition to bed rest, the study also assessed the effectiveness of 37 other clinical interventions, including pharmacological assistance, acupuncture, and mindfulness techniques. Administration of Atosiban (a drug that promotes uterine relaxation) increased the chance of a successful pregnancy by 49 percent, similar to using ultrasound guidance for embryo transfer or having an intrauterine infusion of the hCG hormone, which provided a 27 percent and 23 percent improvement, respectively.

However, a primary limitation of the study is that the findings rely on academically available data, which often leads to a publication bias effect, potentially inflating the significance of certain interventions. 

Acknowledging this, Dr Al Wattar stated, 'While the current body of evidence remains imprecise for these additional interventions, they should not be offered routinely to all couples undergoing IVF pending further research to evaluate their effectiveness and safety.' Furthermore, the authors discourage the clinical incorporation of new and experimental techniques, such as endometrial scratching, prior to well-designed randomised control trials.

The study was published in Human Reproduction Update.

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Welcome to this episode of the I3 podcast where we go Beyond the Webinar, and we continue our focus on UKRAINE here at the International IVF Initiative.

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We’ve been following the amazing efforts of three Ukrainian embryologists and their teams to safely move frozen gametes and embryos out of UKRAINE and if you haven’t heard the previous episode do go back and have a listen. 

First up you’ll hear the pre-meeting chat with Dr. Jacques Cohen and Giles Palmer from I3 and panelists Dr. Pavlo Mazur, Dr. Uliana Dorofeyeva, Olena Novikova and Dr. Olga Chaplia 

What was discussed: 

• What to do from the embryologist aspect, what do you do as a cynic and how to you prepare for tomorrow, next week, next year.
• The gravity of the situation - this has never happened to embryologists before. 
• Perception of people in Ukraine people not being treated like other Western counties - treated like white trash. 
• Why Ukrainian clinics have flourished over the years, talented staff, high education level in Ukraine, lot of interest in Biology and Medicine. 
• Why does this not happen in Hungary or Poland which are EU countries 
• How easy it is to import instruments for IVF such as time-lapse machines or disposables
• How almost all clinics are privately owned - not regulated by the government so they can petition for money to be spent to stay up to date. 
• Discussion about clinics in the US in comparison 
• Tim Sharpe - Conflict expert talks about appearance of Dewers could raise alarm with military personnel at the Border. 
• The enormous global response to what has happened to these Ukraininan embryologists who have been displaced by the conflict and a huge uptake from industry leaders to help this highly skilled group find jobs. 
• How sister clinics and those in neighbouring countries have been reaching out to help, and patent support has been maintained, despite clinics having to close.  

The recording from this session will be available here

Watch the previous session with Tim Sharpe

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Join Denny Sakkas PhD and Keshav Malhotra MBBS MCE for this webinar!

This webinar is intended to provide viewers with an in-depth overview of the optimal use of an electronic witnessing system, how it can minimize and detect potential errors, and how it can be a tool in the traceability and management of the work in an ART laboratory.

Note: all participants will get a certificate of participation

More information and registration via the below link

Tuesday, 15th March, 2022. 3pm EST/ 7pm UK/ 8pm CET / 9pm Kyiv
NOTE TIME CHANGE FOR SOME TIMEZONES

Moderators:
Dr. Jacques Cohen, Dr. Mina Alikani and Giles Palmer

Panellists:
Dr. Pavlo Mazur
Dr. Birol Aydin
Dr. Uliana Dorofeyeva
Olena Novikova
Dr. Olga Chaplia 
Natalie Silverman
Tim Sharp

VIEW HERE

A new preclinical study using human tissue grafted into mice has indicated that high levels of anti-Müllerian hormone (AMH) may contribute to fertility problems and other symptoms associated with polycystic ovary syndrome (PCOS). 

The study, published in Science Advances, found that AMH may result in follicles, the fluid-filled sacs that contain developing eggs in the ovaries, maturing too quickly, affecting ovulation. Previously, it was assumed high AMH levels in women with PCOS were purely incidental and did not play a role in causing the symptoms of the syndrome. 

'AMH is routinely measured in the clinic to give an indication of how many follicles a woman has growing in her ovaries, and this value is often high in women with PCOS. But no one has ever determined whether a high level of AMH, by itself, can have a negative influence', said Dr Daylon James, assistant professor at Weill Cornell Medicine, who led the study.

Follicles support the growth of developing eggs, known as oocytes. Normally, the oocyte matures as the follicle grows, until a mature egg is released from the follicle during ovulation. 

In the 10 percent of women with PCOS, the ovaries contain many small follicles, all of which produce AMH and collectively cause levels to rise. These follicles fail to mature, and when no egg is available for ovulation fertility problems result.

To investigate the role of AMH in PCOS, the research team grafted ovarian tissue from human organ donors with no history of fertility problems or PCOS onto immunocompromised mice. Half of the mice were also transplanted with cells that continuously supplied AMH to the grafted ovarian tissue. The other half were transplanted with control cells, with no AMH. 

The researchers found that ovarian tissue exposed to high levels of AMH contained follicles showing signs of a much later stage of development. This suggests that the presence of many small follicles in the ovaries of PCOS patients are the accumulation of follicles undergoing rapid maturation which fail to ovulate. 

'AMH is causing the usually coordinated growth process between a follicle and its resident oocyte to fall out of synch', said Dr James. 'It is like baking with the oven too hot. The outside, or the cellular component of the follicle, is overcooked, while the inside, or oocyte, is not done', he said. 

Despite the high prevalence of PCOS, the causes behind it are not well known. While some genetic risk factors have been identified, their impact on fertility and diagnosis of the condition remains controversial. 

Although treatments exist for the various symptoms of the disease, they often persist until women reach the end of their reproductive lifespan. The findings of this study suggest that AMH might contribute to the accumulation of follicles found in PCOS, as well as the other secondary symptoms commonly observed. 

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Full-term mouse offspring were derived from single unfertilised eggs using targeted CRISPR/Cas9 epigenome editing.

Parthenogenesis – generating offspring from a single unfertilised egg – is usually not possible in mammals due to a phenomenon known as genomic imprinting. Genomic imprinting describes how methylation in certain regions of the genome silences one allele inherited from either the mother or father, but not the other. These regions are often important for genetic control of embryonic development, which cannot go ahead without correct imprinting.

Now, scientists from Shanghai Jiao Tong University in China have described how they achieved parthenogenesis in a mouse who survived to adulthood and later gave birth to viable offspring by targeting these regions. 

In the study published in the journal Developmental Biology the authors wrote: 'Together, these data demonstrate that parthenogenesis can be achieved in mammals by appropriate epigenetic regulation of multiple imprinting control regions. This is consistent with the famous parental conflict hypothesis (also known as the Haig hypothesis), which proposes that the imprinting-mediated balance between paternal and maternal genomes is critical for mammalian development.'

Seven imprinting control regions of DNA were targeted for induced methylation or demethylation in the study. These targeted imprinting control regions were shown in the literature to play key roles in the regulation of fetal and postnatal growth as well as support the development of bimaternal and bipaternal embryos.

Eggs were removed from a donor mouse and injected with multiple single guide RNAs attached to either Cas9 or messenger RNA that induced methylation or demethylation in the imprinting control region, respectively, in one allele of each gene and not the other. These edited regions maintained methylation during the early stages of development. Quantitative real-time PCR was used to assess the expression of the modified gene in the embryos and suggested that the techniques significantly improved parthenogenetic development. The modified embryos were then transferred into the uteruses of different mice. 

Of 192 embryos transferred at the blastocyst stage, 14 developed into pregnancy, three gave birth, and only one survived to adulthood. Of the two pups who died within 24 hours of birth, further testing demonstrated that at least one of the seven imprinting control regions exhibited loss of methylation confirming imprinting at all seven regions was crucial for development and viability. 

Identifying and editing additional imprinting control regions could improve the efficiency of the parthenogenetic process, the authors suggested. Epigenetic imprinting may also result in unknown off-target effects. Here, off-target analysis of likely sites showed no significant changes, suggesting high-specificity of the technology. Although, future studies are needed to fully assess any effects.

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