Next decade of assisted human conception: a bright future

Excitingly, at this moment in time we are on the verge of several new major advances in gamete and embryo culture, selection and diagnosis.

INFERTILITY affects up to one in six couples worldwide, and in vitro fertilisation (IVF) is a main treatment for such conditions, with over 2.5 million cycles of IVF being performed each year around the world.

Since the birth of the first “test tube baby” in 1978, there have been numerous developments in the field of assisted conception. The advent of intracytoplasmic sperm injection (ICSI) in 1992 helped to alleviate male factor infertility, while the development of blastocyst culture and transfer in the late 1990s – in which embryos were grown for 5 days in order to synchronise developmental stage with the uterus – paved the way for single embryo transfers and higher pregnancy rates.

However, during the first decade of this century relatively little innovation was introduced into the IVF laboratory. Conversely, in the past decade, new developments in incubator technology with built-in microscope capacity have led to the introduction of time lapse technology, whereby one can assess the development of the human embryo in the laboratory every 10 minutes without the need to remove it from the incubator. This breakthrough has not only contributed to higher pregnancy rates but has also provided us with unique access to events during the first week of human life.

Historically, embryos at the blastocyst stage were graded using an alphanumeric system known as the Gardner grade. Although this grading system has proven to be predictive of development and pregnancy, it only assesses the embryo’s morphology at one distinct time point, typically on day 5. With the advent of time lapse it is now possible to look at all stages of development and to develop algorithms to assist in embryo selection. However, although such algorithms use more than one time point, they are typically based on only nine different discreet time points that denote key developmental events, including the times when cells divide. Consequently, the majority of information acquired using time lapse is not used.

With the application of artificial intelligence (AI) it is now possible to maximise and review this massive amount of data – far more than any human could ever process – using deep learning and neural networks, facilitated by supercomputers. To date, this approach appears to be as good as an expert embryologist in selecting a blastocyst for transfer (and here) and reduces the variability between embryologists making their subjective analysis of the embryo. A large prospective randomised trial (ACTRN126220000197932) across Virtus Health’s IVF clinics in Australia, the UK, and Denmark is being undertaken to determine if using AI for embryo selection in human IVF results in an equally as high clinical pregnancy rate compared with trained embryologists using standard morphology criteria.

Excitingly, the use of AI in human IVF is currently being expanded across several aspects of a treatment cycle.

This includes the capacity of AI to undertake sperm selection, identify embryos at greatest risk of being aneuploid (having an abnormal number of chromosomes in a haploid set), facilitate real-time feedback on laboratory performance (thereby increasing efficacy), and assist with the day-to-day management of ovarian stimulation.

However, AI is not the only exciting technology being researched to advance human infertility treatment.

Microfluidics – the movement of submicrolitre volumes in specifically developed chips – is a rapidly developing area of engineering and appears to be well suited for sperm processing and selection. Such devices have the capacity to have built-in diagnostics all contained within the one microdevice.

In parallel to this technology, advances in microfabrication using novel three-dimensional (3D) printing technologies is providing the opportunity to create dynamic culture environments for the embryo as it develops and differentiates. Furthermore, new 3D devices could also pave the way for the automation of procedures, including ICSI.

While time lapse technology has been able to maximise the use of embryo images it cannot directly quantitate the physiology of the embryo, which is smaller than a full stop on a printed page.

Developments in biomarker analysis, which are based on sampling the surrounding media in the culture dish, and are therefore completely non-invasive, have revealed that nutrient consumption by individual embryos is positively correlated with transfer outcome. New advances in optical microscopies are also being evaluated to assess the metabolic state of embryos. As we start to obtain more information about the physiology and morphology of the developing human embryo, AI will again be used to help create algorithms to better predict transfer outcomes.

I have had the honour of working in embryology and IVF for 40 years and have overseen the development and translation of new technologies into assisted human conception. Excitingly, at this moment in time we are on the verge of several new major advances in gamete and embryo culture, selection and diagnosis. The culmination of these new innovations should help us to better diagnose male infertility, improve the efficiency of ICSI, and increase embryo development and hence pregnancy rates, helping to reduce the time to a healthier pregnancy, and to give patients the best chance of getting pregnant the first time.

The future of IVF is extremely bright.

Professor David K Gardner AM is Scientific Director of Melbourne IVF and Distinguished Professor in the School of BioSciences at the University of Melbourne. He receives research funding from Vitrolife AB, Sweden. He is a CI on the trial investigating AI and embryo selection.

The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policy of the AMA, the MJA or InSight+ unless so stated.

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