54 CLINICAL FOCUS
54 CLINICAL FOCUS
3 NOVEMBER 2023 ausdoc . com . au
Therapy Update
Conceiving the future of ART
Reproductive medicine
Professor David K Gardner is the scientific director of Melbourne IVF and a distinguished professor in the school of biosciences at the University of Melbourne .
New technology supporting IVF will see key advances in the next decade , leading to increased success and availability of infertility treatment .
ASSISTED reproductive technology continues to be a rapidly evolving field of medicine .
Several new technologies are being developed and evaluated to improve both the efficiency and efficacy of human IVF . The key areas that will be implemented over the next five years will include the introduction of novel micro devices for sperm preparation and diagnosis , and assisted fertilisation , embryo culture and cryopreservation — all made possible through breakthroughs in microfluidics and 3D printing . Additionally , microrobotics and automation , and analysis of biomarkers of embryo health will be introduced . All of which will be combined with the increased use of artificial intelligence ( AI ).
This article reviews some of the embryological advances that are likely to make their way into assisted reproductive technology ( ART ) practice in the coming decade .
IVF today
The embryological methodologies used in human IVF have changed little in the past 40 years , requiring highly skilled professionals to perform numerous tasks manually .
This means the success of each step , such as injecting a single sperm into an egg , is dependent upon the skill set of the individual embryologist . When it is time to select an embryo for transfer to the uterus , a subjective assessment of embryo morphology is undertaken , aided by the application of grading systems . Although all embryologists are highly trained , there is still potential for interoperator variability , especially when it
comes to visual assessment of embryo morphology . With a dramatic increase in new technologies and AI being developed outside assisted human conception in recent years , the time has arrived for them to be evaluated in human IVF .
Future developments
SPERM SELECTION With a significant global decline in sperm counts and quality , there is an ever-increasing need to better assess sperm health . Currently , sperm are prepared by washing in IVF media followed by centrifugation . If assisted fertilisation is required through the injection of a sperm into an egg — a process known as intracytoplasmic sperm injection ( ICSI ) — the sperm is selected manually based on its morphology , which does not occur in conventional IVF .
The embryological methodologies used in human IVF have changed little in the past 40 years .
With the development of microfluidic devices based on biomimetics — namely , devices designed to mimic the convoluted epithelia of the oviduct and hence promote the swimming of healthy sperm — sperm can be processed more rapidly and have been found to have lower levels of DNA damage , resulting in better pregnancy outcomes . 3
Further , advances in laboratory -on-a-chip ( in which sub- µ L volumes can be controlled using microfluidics and subsequently analysed ) mean whole semen analysis on a chip is rapidly becoming a reality . 4 With this approach , not only will it be possible to process and evaluate sperm , but it will also be feasible to analyse other components of semen , such as small extracellular vesicles , which have important roles in sperm function and consequently both therapeutic and diagnostic potential .
AI is currently being tested in assessing the morphology of sperm and will be used in the future to identify sperm in testis biopsy samples . 5 The latter process is extremely time-consuming , requiring several hours of an embryologist ’ s time to identify the few sperm present in a biopsy . 5 Recent work , presented at the European Society of Human Reproduction and Embryology in June , reported that AI could reduce the time taken to scan a slide from hours to just 10 seconds , with a precision of more than 90 %. 5 , 6
FERTILISATION , EMBRYO CULTURE AND CRYOPRESERVATION With the advent of 3D printing using two-photon polymerisation , it has been possible to fabricate devices with micron levels of accuracy to house and culture individual oocytes and embryos in a more physiological and dynamic fashion . 7 This offers the capacity to provide for the changing needs of the embryo in real time as it develops , helping to
NEED TO KNOW
Since the birth of the first test-tube baby in 1978 , more than eight million children have been born via IVF . 1
Currently , 5 % of all children born in Australia are conceived through IVF . 2
The demand for assisted reproductive technology worldwide is increasing , driven by the deferment of having children until later in life ( maternal age over 35 ), a global decrease in sperm counts and sperm quality , and an increasing demand for oocyte cryopreservation by women in their 20s and early 30s .
The technology supporting IVF is at a tipping point , and we are set to witness a number of key advances in the next 10 years .
improve embryo development . 8 Indeed , this approach has now been used for ICSI and cryopreservation of oocytes and embryos . 9 , 10 In the case of the former , the 3D device induces less stress on the oocyte during the sperm injection process , ultimately leading to reduced egg degeneration and more successful outcomes . Furthermore , the microfabricated device significantly reduces the time it takes to perform the sperm injection procedure .
EMBRYO ASSESSMENT With the advent of time-lapse incubation technology , it is now possible to image the embryo every 10 minutes within the incubator rather than simply looking at the embryo at discrete times during its development before transfer . This creates an enormous amount of video data for each embryo . To maximise the use