Research Archives - Aria Fertility

Everything you wanted to ask an embryologist: part two

Embryologists perform an essential role throughout the patient pathway at an IVF clinic. As well as their lab work, they also regularly interact with patients. In part two of ‘Ask an Embryologist’, Senior Clinical Embryologist Kim Hill answers your most frequently asked questions, including how often you will hear from your embryologist.

“We speak to patients in general every other day, typically after the fertilisation check, then on day three and day five. Obviously, some people prefer not to hear from us during that time and just want to know the final outcome, which is fine. Some people want to speak to us every day. It depends on how the patient feels and what support they need.”

What is the difference between a day three embryo and a blastocyst?

At day 3, it should have about six to eight cells. When it becomes a blastocyst, it makes different cell types and expands. You can usually start to see a small cavity forming by the end of day four, and by day five, you would hope to see a nicely expanded blastocyst with clear cells inside. It usually reaches that stage on day five or day six, but it can even be from day 7.

Why do so many embryos stop growing after day 3 and not make it to day 5?

Most fertilised embryos reach the day 3 stage, as the egg drives development until that point. The drop-off from day 3 to day 5 is when the egg and sperm fuse, creating a new genome. This process requires a lot of energy.

If it reaches the blastocyst stage, we know it’s overcome a major hurdle in the embryo’s growth.

Only about 40 to 50% of embryos make it from fertilisation to day 5 stage, so it is essential to prepare patients for this.

Is there anything that could address this in the future?

Unfortunately, IVF is a numbers game, which is why the patients go through the stimulation process because we want to start with as high a number as possible.

Techniques will hopefully be developed in the future to address that drop-off. Artificial Oocyte Activation (AOA) with Calcium Ionophore is currently being investigated, although more research is required to determine its benefits for patients.

When my embryologist talks about normal fertilisation the day after my retrieval, what does that mean?

A newly fertilised embryo will have one small circle for the egg and one small circle for the sperm. That is what we call a Pronuclear (2PN) embryo. Sometimes, you can get a 1 PN or 3 PN embryo, and this usually indicates that something isn’t right. For example, three circles could indicate that two sperm fertilised the egg at the same time during IVF, which means there is too much genetic material in there, and it’s likely that that embryo will be abnormal.

What is assisted hatching?

Assisted hatching is a technique that we use to help the embryo hatch out of its hard outer shell. When the embryo is small, it has a thick layer of protein around it and when it’s ready to implant, it normally hatches out of this shell.

A small incision is made using a laser. Sometimes, we may do this if the embryo can’t hatch naturally, but often, we do it if we need to do a biopsy. At that point, the embryo is hundreds of cells, and this helps us get a couple of cells from the outer layer with the least manipulation as possible.

What is PGT-A?

PGT-A is pre-implantation genetic testing for aneuploidy, and more and more patients are opting for it compared to three to five years ago. It checks the number of chromosomes inside the embryo.

The Aria consultant will discuss this with them initially but often they are receiving a lot of information at this stage, so we will also discuss this with them during the decision-making process.

Can my embryo be damaged during the PGT biopsy process?

Anything that requires embryo manipulation is risky, but I would say the risk here is very low, under 5%. The process requires us to remove three to five cells from the embryo, but at this point, it has hundreds of cells, and we know it can regenerate those cells quickly as long as the quality is sufficient.

It requires quite a bit of training on our part because you are taking cells from the outside, which are the placenta cells, rather than the inner cell mass.

How is sperm quality assessed?

Sperm quality is taking a front seat compared to ten or fifteen years ago. There has been a decrease in sperm count worldwide, and there has been much research into the role of lifestyle factors, such as our sedentary lifestyle, diet, stress, and pollution.

We assess the sperm under a microscope, looking at the number of cells we can see, how they move, and how they look. We use certain criteria to determine whether we can proceed with IVF confidently, knowing that there’s a good chance of fertilisation.

If it doesn’t quite meet those criteria, we recommend ICSI, which bypasses the swimming process.

How much does sperm DNA fragmentation affect the quality of embryos?

Sperm DNA fragmentation is linked with poor embryo development and quality and is being taken more seriously now. We can perform a test to determine the damage or ‘fragmentation’ of the strands of DNA held inside the sperm head. This can be genetic but can also be caused by several factors, including lifestyle choices, environmental factors, and health issues.

More questions? Call +44 (0) 203 263 6025 or email us at admin@ariafertility.co.uk to arrange a consultation at Aria Fertility.

26 February 2025/by CLINIC TEAM

Everything you wanted to ask an embryologist: part one

FAQs, News, Research

The role of an embryologist is central to the success of an IVF cycle, requiring an exceptionally high level of skill and focus to nurture life at its earliest stages. However, embryologists don’t only work in the laboratory; they also regularly communicate with patients, helping them understand the lab side of their treatment.

Kim Hill, Senior Clinical Embryologist at Aria Fertility, answers the questions they get asked most frequently: “We try to guide the patients through the decisions they will have to make, help them understand what to expect in terms of outcomes, and manage their expectations.

My embryo was abnormal; why did you freeze it?

Even embryos that look good in the lab and have good grading may have defects not visible to the naked eye.

If an embryo undergoes PGT-A testing, we must freeze it while we wait for the results. When the embryo is grown to the blastocyst stage, we do the biopsy procedure, where we remove a few cells, but then we must freeze the embryo while we wait for those test results, which can sometimes take about two weeks to come back.

Another reason would be that the patient wishes to test embryos further. So, if the embryo was frozen and they wish to do genetic testing at a later stage, then we would thaw the embryo, biopsy it, and then refreeze it. Unfortunately, it could then come back as abnormal.

How long do frozen embryos last?

From a biological standpoint, embryos preserved through modern vitrification techniques can be maintained indefinitely, provided they remain frozen. We know that quality doesn’t decrease, and survival rates are good.

Legally, the current rule is that gametes or embryos can be stored for up to 55 years, but you will need to renew your consent every ten years. Some patients choose not to consent for the full ten years, so we must go through the renewal process with them and discuss their options at an earlier stage.

What is the likelihood of embryos not surviving the thaw?

Unfortunately, it does happen, although not very often. Our in-house survival rates are about 98% and so we are confident in our freeze and thaw protocols. Thorough training is involved to reach competency and this is important to maintain that high rate.

The embryo grade is a description of how robust it is to survive the freeze and thaw processes.. If an embryo is only borderline quality, we must discuss it with the patient(s) so they understand it might only have lower survival rate. It’s about clear communication and an empathetic approach with the patient.

We have a cut-off criterion for embryos, and we are as transparent as possible. Our role is to ensure patients have all the information they need to make this decision. Every patient’s journey is different, so it is never a one-size-fits-all situation.

Are frozen transfers more successful than fresh ones?

Our rates are pretty similar between fresh and frozen transfers. A fresh transfer means they collect the eggs, quickly followed by the implantation, which is a lot for the body to go through. Whereas a frozen transfer means you can let your body recover after the stimulation cycle.

Is the size of the follicles linked to egg/embryo quality?

It’s difficult to predict which eggs will come from which follicles. In general, you are more likely to expect more mature eggs from bigger follicles, but sometimes they can be empty, and sometimes we get mature eggs from smaller follicles as well. Our doctors always aim to get as many eggs as possible.

How do you grade embryos?

We get a lot of questions about this because we give our patients a report which outlines the quality of the embryos. Aria employs the Gardner Grading Scale, the most common and universally used blastocyst grading system.

It has three parts: the expansion of the embryo, the Trophectoderm (TE) layer quality, and the inner cell mass (ICM) quality.

This means that at your blastocyst-stage, depending on how expanded the embryo is, you can usually see the two cell types. The trophectoderm is the outer cells, which become the placenta, and then you have the inner cells, or the baby-making cells.

The Gardner Blastocyst Grading System:

Number (1 to 6)- Blastocyst development stage – expansion and hatching status.
First letter (A to C)- Inner cell mass (ICM) quality.
Second number (A to C)- Trophectoderm (TE) quality.

Aside from grading, how do you choose which embryo to transfer?

If a patient has multiple embryos of similar quality and hasn’t been tested for genetic status, we use a few scoring systems.

AI algorithms are built into our embryoscope, our time-lapse incubator. We use the KIDScore™, which tells us the embryo’s potential for implantation based on a large amount of data from multiple clinics. We also have something called the iDAScore, which predicts the chance of achieving a clinical pregnancy based on the detection of a foetal heartbeat.

We also use the ERICA (Embryo Ranking Intelligent Classification Assistant), an AI system that ranks embryos based on their chance of being euploid or genetically normal.

Our success rates are based on the clinical data we’ve collected over the years, and these multiple systems are tools for applying this data quickly to help with embryo selection.

If we’re doing a fresh transfer, you have to make the decision relatively quickly (day 5 of embryo development). If it’s a frozen transfer, you have from the point they start taking their luteal support medication, so we have a couple of days to decide. We usually have a team discussion, and we also like to consider the patient’s choice.

More questions? Call +44 (0) 203 263 6025 or email us at admin@ariafertility.co.uk to arrange a consultation at Aria Fertility.

24 February 2025/by CLINIC TEAM

The Blend of Human Expertise and AI in IVF

News, Research

Have you ever wondered how technology is transforming the world of IVF? At Aria, we combine human expertise with the power of artificial intelligence (AI) to help create families.

Embryologists are the unsung heroes of the IVF process, but their human ‘AI’ does not develop overnight. Their keen eyes and skilled hands result from years of experience, which allow them to make judgments based on a multitude of knowledge points derived from their extensive training and practice.

The role of AI in IVF: enhancing decision-making

In our lab, AI is not just a tool but a trusted partner. AI is used to analyse imaging data – pictures and videos of the precious cells that we hope will become a success story one day. This data is processed to generate scores that help us assess quality.

When evaluating AI algorithms, and there are lots of them nowadays, we ask critical questions: How large and diverse was the dataset used? What type of microscopes or images were involved? Was the data static or dynamic, 2D or 3D? What is the accuracy of the predictions? Are they developed to predict pregnancy chances, live birth rates, or genetic makeup?

These questions ensure that the AI tools we integrate are reliable. Ultimately, the embryologist makes the final decision, guided by both the AI’s recommendations and their expertise.

Aria’s own studies

AI’s role in the fertility lab has been much in the media spotlight. UK researchers recently published a study in Nature Communications that explored which follicle sizes were associated with improved rates of retrieving mature eggs, resulting in babies being born.

The scientists at Imperial College London used ‘Explainable AI’ techniques – a type of AI that allows humans to understand how it works – to analyse retrospective data on more than 19,000 patients who had completed IVF treatment.

One of the challenges with AI is the ‘black box’ nature of many algorithms. This means that while AI can provide scores and recommendations, the reasoning behind these decisions is not always clear.

At Aria, as scientists, we are committed to understanding AI processes. For instance, we used an AI tool to assess single-sperm motility variables related to ICSI practices but went a step further and looked for biological reasons (in this case, sperm maturation properties) to support the ranking we were given.

We tested AI systems designed to predict the genetic makeup of embryos and their chances of implantation. How? Because we use time-lapse technology, we collect thousands of images, providing a comprehensive view of development. The AI can then analyse these images in a single second, identifying patterns and making predictions that would be impossible for a human to do in such a short time. But are these, on their own, better? The jury’s still out.

“Something key is to understand why an embryo is deemed good by AI,” says Aria’s Senior Clinical Embryologist and Laboratory Manager Dr Xavier. “This knowledge will help us refine our processes and make IVF more efficient.”

While AI offers tremendous benefits, it also raises ethical and practical considerations. We ensure that the AI tools we use are reliable, maintaining a balance between human expertise and technological support. This approach guarantees that our patients receive the best possible care.

Founding director of Aria Mr Stuart Lavery concurs. A well-respected member of the global human fertility community with over 20 years’ experience providing fertility care and support, he believes, “AI represents an amazing opportunity that could impact on improving laboratory results, optimising clinical decision making and enhancing our patient’s experience.

“There is no doubt that its potential will be best realised not by replacing doctors and scientists but by supporting their decision making.”

AI systems have run quietly in the background from the start, always ready to provide an immediate second opinion. They are our copilots, enhancing our decision-making process and ensuring that every choice we make is backed by the best possible data and insights.

29 January 2025/by CLINIC TEAM

Aria embryologist Dr Xavier Vinals Gonzalez publishes preimplantation genetic testing research

News, Research

At Aria Fertility, we believe in empowering our patients with knowledge and support to make informed reproductive decisions. Our commitment to patient education is at the heart of everything we do. Recently, our head of the laboratory, Dr Xavier Viñals Gonzalez, in collaboration with University College London, published a study on patient perspectives after preimplantation genetic testing for aneuploidy (PGT-A). This research sheds light on the complexities and challenges faced by patients when deciding whether to transfer a non-euploid embryo. Today, we sit down with him to discuss the findings and their implications for patient care.

Dr Gonzalez, can you explain what non-euploid embryos are and why they presents a challenge in reproductive medicine?

Dr X: When we perform preimplantation genetic testing for aneuploidies or PGT-A, we typically would expect to get embryos reported as euploid (genetically normal) or aneuploid (genetically abnormal). Mosaic or segmental aneuploid embryos are non-euploid embryos which have shown to have moderate to good reproductive potential based on published literature. When a non-euploid embryo is identified, the decision to transfer such embryos offers challenges to patients as the clinical outcomes and long-term effects are often uncertain.

Your study highlights several key factors influencing patient decision-making. Can you elaborate on these?

Dr X: Certainly. Our study involved an online survey of individuals worldwide who had undergone PGT-A during their fertility journey and had a non-euploid embryo as a result. For most respondents, the type of non-euploid found was a mosaic. From their responses, we learned that the opportunity to discuss implications, the number of topics covered during consultations, and the country where the treatment was received were significant factors influencing decision-making. Additionally, respondents highlighted mismatched expectations, inadequate information provision, and an unsupportive decision-making process as major challenges.

Can you share some of the respondents’ experiences regarding mismatched expectations of PGT-A?

Dr X: Many respondents noted a gap between how IVF professionals explain PGT-A to patients and the certainty with which it is offered. Quotes in the paper reflect a common sentiment that the limitations of PGT-A may not have adequately been communicated.

How common is mosaicism in human embryos?

Dr X: This is a very good question and the answer may vary depending on which clinic you will be undergoing treatment and the genetic laboratory that will process your samples. However, we would typically expect the mosaicism rate to fall under 10% across all age groups. Not all clinics report mosaicism, so if this information is important to you – this is something you will need to discuss with your team.

What about the clinical outcomes of mosaic embryos?

Dr X: In recent years, research in mosaic embryos has shown similar reproductive outcomes compared to embryos reported as euploid – and by outcomes, I mean sustained pregnancy/live birth and miscarriage rates. One of the main concerns I hear from patients is how likely is this mosaicism seen on embryos to be present at birth; and from what we know, this is very unlikely. It is important to also note that there are different types of mosaic and other non-euploid embryos (ie. non-mosaic segmental), with varying outcomes. We are very active in the area of human reproductive genetics and we hope to share the work we are doing soon.

Respondents also mentioned inadequate information provision from clinics. Can you discuss this issue?

Dr X: Yes, some respondents expressed that their clinics provided limited or no information about PGT-A ahead of the testing. Less than a quarter of the respondents were given information about the use of non-euploid embryos and only 17.5% were aware of the risk of miscarriage after PGT-A. One respondent said, “There was no discussion other than it was included into the IVF package.” This lack of detailed information led many patients to undertake their own self-directed research, often relying on medical literature, peers, private genetic counsellors, and social media groups.

How does Aria address these concerns?

Dr X: At Aria, we are committed to providing comprehensive and transparent information to our patients. We believe in clear, patient-centered communication to help patients understand their options. Our team is available to discuss the implications of PGT-A results and answer any questions. We strive to create a supportive environment where patients feel empowered and informed. We have an excellent Genetic Counselling support service that explores complex genetic information with patients so they can understand some of these terminologies in the context of current evidence in the field.

What are the global trends and insights from your study?

Dr X: It’s important to note that the data in our study comes from patients worldwide, with a higher proportion of respondents having received treatment in the US. This highlights global trends and could provide insights into how different populations navigate non-euploid embryo transfers.

What are the next steps for research in this area?

Dr X: The field of reproductive genetics (and embryology) is continuously evolving. Studies on non-euploid embryos, show that some previously not recommended for treatment could now be considered after careful consideration. The eldest baby born from a mosaic embryo in our dataset was 3 years old at the moment of response and met all developmental milestones. Research on live birth data and developmental milestones could bring further reassurance to patients and professionals. Our research highlights the need for further studies to better understand the experiences and needs of specific patient groups. By expanding our understanding, we can continue to improve the support and information we provide to our patients. We are committed to advancing reproductive medicine and ensuring our patients have the best possible care and support.

Thank you for sharing these insights. Any final thoughts for our readers?

Dr X: At Aria, we are dedicated to helping our patients navigate the complexities of human reproduction with information based on internal evidence and experience, considering global trends. It is part of our human nature to want to quantify success in numbers, and with the broad information we have online nowadays it is difficult for patients to gather whether that is relevant to them or not. If you have any questions or need more information about genetic testing, please don’t hesitate to reach out to our team.

Click here to read the research in full >

For more advice on preimplantation genetic testing for aneuploidy (PGT-A), call +44 (0) 203 263 6025 or email admin@ariafertility.co.uk to arrange a consultation with one of our fertility experts.

25 November 2024/by CLINIC TEAM