Advancements and Challenges in IVF on the 40th Birthday of Louise Brown

An Interview with Dr Dean Morbeck

Written by James Coker  |  Reporter, European Medical Journal  |  @EMJJamesCoker

On this day, 40 years ago, the first baby was born after conception by in vitro fertilisation (IVF), a momentous occasion in the history of healthcare. The birth of Louise Brown in Oldham General Hospital, Manchester, UK on 25^th of July 1978 was the culmination of decades of pioneering work to develop this technique to a stage where it could result in pregnancy in couples unable to conceive by natural means. Since that seminal moment, around 8 million babies have been born around the world following IVF,¹ transforming the lives of millions of people. IVF and assisted reproduction techniques in general have continually advanced since that day, with ongoing work continuously improving the efficacy, availability, and invasiveness of the technique. To find out more about the growth of this area of medicine and the innovations occurring, as well as the challenges that need to be overcome in the future, the EMG spoke to Dr Dean Morbeck, a renowned expert in fertility treatments. Dr Morbeck is Scientific Director at Fertility Associates, in addition to lecturing at the University of Auckland, Auckland, New Zealand. This took place during this year’s Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), held from 1^st–4^th July 2018 in Barcelona, Spain. The event was replete with updates, new research, and insights from expert speakers throughout the 4 days, and will be reviewed in the upcoming edition of the EMJ Reproductive Health eJournal, published in August.

Advances in IVF

Dr Morbeck has always had a substantial professional interest in finding ways to enhance the many steps involved in the IVF procedure. “I started in private practice in the mid-90s and spent about 10 years in small private practices throughout the USA where I saw many inefficiencies in the way we do IVF and how we help patients,” he elucidated. “What I realised was that there were a lot of areas that needed improvement, so then I went back to the Mayo Clinic in 2005 and was able to start doing research on methods of improving the quality of the process to make it better and have better outcomes. That was the driving passion for me; to improve this process and the things I see on a day-to-day basis. So, I’ve been successful in identifying areas that could be improved and how to improve them. There have been small incremental advances, and there have also been other amazing changes that have occurred in the last 20 years that have really changed the face of IVF.”

One of the most ground-breaking advancements in Dr Morbeck’s view has been the use of blastocyst culture, which has enabled enhanced embryo selection by being able to culture them up to 5 days, compared to the typical 3 days. This has led to major benefits for those patients in whom this technique can be utilised, including the reduction in multiple births that sometimes occur after IVF.² Another development he identified was the intracytoplasmic sperm injection (ICSI) technique, which can be utilised in cases in where natural conception is impossible because the man has a very low sperm count or no sperm at all.³ In more recent years, the shift towards vitrification for freezing embryos is a trend that Dr Morbeck views as especially important.⁴

Culture Media

There are a number of areas Dr Morbeck is currently working on to enhance the field further. One of these is the use of culture media to support embryo development. In a presentation at the ESHRE congress entitled ‘Composition and performance of commercial media for IVF’, the Kiwi doctor gave an overview of the performance of different types of culture media and the improvements that can be made to improve outcomes. One challenge has been the effect of culture media on birthweight, with little evidence why babies born following IVF are lighter on average.⁵ He would therefore like to see more research being carried out to better understand such issues, although he acknowledged that the complex nature of this area makes this difficult. “What we really need in the area of culture media is more randomised controlled trials (RCT) comparing two culture media in several clinics so we can see if there is a difference in birth weights and neonatal outcomes,” he elucidated. “We have very few of these types of studies and they’re really not that that difficult when you compare them to other RCTs. So, laboratories could be doing more of these and we’re looking forward to doing one in New Zealand.”

Importance of Air Quality

Dr Morbeck has also conducted a significant amount of research looking at the causes of stress in pre-implantation embryo culture. In a presentation at the ESHRE Congress entitled ‘Extrinsic factors disrupting embryo homeostasis’, he listed a number of external factors that impact culture systems and he picked out the influence of air quality as an area in which knowledge is advancing rapidly.⁶ This is now bringing greater attention to the need for good air quality in IVF facilities. Dr Morbeck explained: “When we talk about air quality, we think of two things: we think of particles that could cause a contamination, and we also think of reactive compounds, such as volatile organic compounds (VOC) and fumes from diesel or exhaust. While both are important, we need to pay special attention to VOCs.”

To help spread awareness, Dr Morbeck recently participated in the creation of a consensus document outlining the importance of good air quality in assisted reproduction technology (ART) facilities and how this can be achieved. Published earlier this year, the document is entitled: ‘Cairo consensus on the IVF laboratory environment and air quality: Report of an expert meeting’. It includes recommendations on site suitability, design criteria for building construction, and laboratory commissioning and ongoing VOC management.⁷

Time-Lapse Imaging

A particularly interesting area for Dr Morbeck is the use of time-lapse imaging for monitoring the development of IVF embryos before they are transferred to the womb; this is becoming an increasingly recognised method of selecting the embryo most likely to result in pregnancy.⁸ “Time-lapse is a favourite of mine; any embryologist who’s used time-lapse imaging is a huge fan because it just intuitively makes sense to culture embryos where you don’t disturb them, you leave them alone, but you get more information,” he commented.

However, there has so far been a certain amount of resistance to utilising this innovative technique in some quarters, preventing its use on a wide scale. Dr Morbeck believes this is partly because it has brought small, incremental gains rather than large-scale individual advantages that are easily identifiable in large-scale studies. Another is the financial cost to laboratories in purchasing the necessary equipment, which can be hard to justify in the absence of substantial evidence. He argued, however, that there are numerous small benefits that are difficult to quantify but could make all the difference for certain patients. In his view the biggest opportunity in time-lapse imaging lies in the vast amount of information that can be gained from this technology; this in turn enables the potential for other innovative technologies such as artificial intelligence and machine learning to use these data to enhance embryo selection even further.

Happily, he foresees time-lapse imaging becoming far more widespread in the future: “We need more suppliers in the market, and we are now getting to that point,” he explained. “That’s hopefully going to drive the cost down but also give clinics more options to choose from; it’s just a matter of time before clinics completely switch over to time-lapse. I don’t think there really needs to be much of a business initiative to do that, it’s just a matter of natural evolution of technology.”

Increasing Demand?

We also discussed the growth of assisted reproduction in general and the future of this area of medicine. Even despite the advancements that have occurred and will surely continue to take place in the future, Dr Morbeck has not observed any particular trends in regard to couples seeking artificial conception and cannot envisage an era in which people choose this option ahead of natural pregnancy, such as for genetic reasons like trait selection. “I think that because it’s expensive and invasive, it’s never really going to catch on for people that want to do it if they don’t have to,” he said.

Future Challenges

As we reach the 40^th anniversary since the birth of Louise Brown, there are a number of key areas in IVF that Dr Morbeck would like to see further advancements being made in. These include increasing the quality of embryo selection with a fast turn-around for the clinic, as well as developing less invasive methods for measuring blastocyst quality. Ultimately, this will likely necessitate the use of computerised technologies, such as artificial intelligence, that are still in their infancy in this field. He cautioned that care needs to be taken when implementing new techniques and technologies in assisted reproduction to ensure that people in a desperate situation are not subjected to unproven procedures. He warned: “I think we have to be careful when we’re looking at technological advancements because we know that patients are vulnerable, they want to do whatever they can, they’re looking for that silver bullet to make the difference. It’s a challenge and we have to be guarded as we introduce new technologies.”

Dr Morbeck also acknowledged that healthcare professionals in this area are still severely hampered by the quality of patient gametes. “We still have the limitation that if a patient makes eggs or sperm that aren’t compatible with implantation, there isn’t much we can do,” he added.

EMJ Reproductive Health

It was enlightening to hear about the work and opinions of Dr Morbeck in the field of IVF and assisted reproduction more generally. These topics and more were discussed in depth at the 2018 Annual Meeting of ESHRE, and we will be publishing a full review of the event in the upcoming edition of the EMJ Reproductive Health eJournal, available on our website in August. The journal will also include abstract and symposium reviews presented at ESHRE, interviews with leading figures in the field, and a range of peer-reviewed articles. You can subscribe here for free to receive instant news of the publication of this open-access journal.

REFERENCES

1. Scutti S. At least 8 million IVF babies born in 40 years since historic first. 2018. Available at: https://edition.cnn.com/2018/07/03/health/worldwide-ivf-babies-born-study/index.html. Last accessed: 10 July 2018.
2. Johns Hopkins Medicine. Blastocyst Culture and Transfer. Available at: https://www.hopkinsmedicine.org/fertility/services/blastocyst.html. Last accessed: 10 July 2018.
3. Johns Hopkins Medicine. Intracytoplasmic Sperm Injection (ICSI). Available at: https://www.hopkinsmedicine.org/fertility/services/sperm_injection.html. Last accessed: 10 July 2018.
4. Europe IVF International. Vitrification: a new way to safely freeze embryos. Available at: https://www.fertility-ivf.eu/en/methods/vitrification/. Last accessed: 10 July 2018.
5. European Society of Human Reproduction and Embryology (ESHRE). First randomised trial shows IVF culture media affect the outcomes of embryos and babies. 2016. Available at: https://www.eshre.eu/Press-Room/Press-releases-2016/IVF-cultures.aspx. Last accessed: 10 July 2018.
6. Morbeck DE. Air quality in the assisted reproduction laboratory: A mini-review. J Assist Reprod Genet. 2015;32(7):1019-24.
7. Mortimer D et al. Cairo consensus on the IVF laboratory environment and air quality: Report of an expert meeting. Reprod Biomed Online. 2018;36(6):658-74.
8. NHS Choices. Time-lapse technique may boost success rate of IVF. 2013. Available at: https://www.nhs.uk/news/pregnancy-and-child/time-lapse-technique-may-boost-success-rate-of-ivf/. Last accessed: 10 July 2018.