IVF News

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
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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

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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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I THINK I READ IT SOMEWHERE..

Tuesday, 22nd March, 2022. 3pm EST/ 7pm UK/ 8pm CET
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Moderators: 
Dr. Peter Nagy and Dr. Kathryn Go 

Talks and discussions on the backstory of influential scientific papers and hidden gems in scientific journals that defined how we work today.

Dr. Jacques Cohen
Dr. Santiago Munne 
Prof. David Gardner 
Prof. Gianpiero D. Palermo
Dr. Kimball Pomeroy

This session is kindly sponsored by ZyMōt Fertility

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In Beijing, couples using the city public medical insurance scheme, will be insured for 16 different types of fertility treatment, as part of China's response to counteract the country's declining birth rates.

China has continued to see a decline in birth rate despite encouraging couples to have a third child, since the three-child policy was introduced last year. In 2021, the number of births per woman in China was 1.15, which was one of the lowest in the world, according to the Chinese cable TV news service, CGTN.

'The announcement of the policy shows the country's determination to encourage birth,' Liao Xi, dean of Beijing Perfect Family Hospital, told the Beijing-based newspaper, Securities Daily. 'Those who choose assisted reproductive technologies have a strong willingness to have a child. But the success rate of the technologies is limited. The services were previously not included under the public medical insurance scheme because they are costly.'

The insurance will cover fertility treatment, including IVF and intrauterine insemination (IUI) from 26 March, as reported by Chinese state-run Xinhua News Agency. IUI involves sperm being directly injected into the uterus for improved fertilisation success. The number of IVF rounds that couples can have subsidised is also unlimited as reported in the Times.

Some Beijing residents have responded well to this change in policy as reported by the Chinese state-owned online magazine, Sixth Tone. They interviewed 30-year old Luo Yanan, who has spent 50,000 yuan on two unsuccessful IVF procedures, last year. Yanan 'hopes to try the procedure again and is relieved that part of the costs would be covered by insurance.'

This change in Beijing's insurance scheme may spread to other cities as well. An employee from an infertility treatment centre in Shanghai, told Sixth Tone: 'the city is now under pressure to add assisted reproductive technologies to insurance scheme after Beijing's move.'

China is also considering additional measures in easing the burden of child-rearing for families. These includes longer maternity leave and increasing the number of nurseries available.

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