Thoughts and reflections from ASRM 2019

This year Philadelphia hosted the annual American Society for Reproductive Medicine meeting for thousands of delegates from all over the world. Similar to previous years, IVF professionals gathered to present or listen to the latest scientific developments in the field of assisted reproduction. We have collected some of our thoughts and reflections of the scientific content of the meeting in this blog post.

Artificial intelligence on the agenda

It is very interesting to follow how artificial intelligence-based analysis is becoming increasingly investigated for potential use in different aspects during IVF. In total we counted 24 scientific abstracts employing AI approaches for optimising IVF processes, the majority relating to embryo evaluation or selection. As explained by Dr. Hickmann and Dr. Zaninovic in their common Pre-plenary session “Eye on AI: Artificial intelligence in ART” (LET01), embryo evaluation and selection has been the initial focus when implementing the powers of AI because time-lapse monitoring of embryos and the subsequent clinical outcomes provide suitably structured data to develop and train deep learning neural networks. Other areas in ART will likely follow in the future.

Culture conditions are still essential 

A topic that is always of interest is of course how stable culture conditions are the basis of successful IVF. Improved blastocyst development in the EmbryoScope+ versus a benchtop trigas incubator was demonstrated in a poster by Nicolielo et al. (P-44) entitled “Embryo culture in time-lapse system provides better rates of blastocyst formation, decreases embryo development arrest compared to traditional benchtop triple gas culture system”. In this study examining development of 9482 oocytes from 1276 cycles, there was a statistically significant difference in number of blastocysts, mean blastocyst per cycle and a reduction in cancelled cycles. The conclusion was that the uninterrupted culture available with the time-lapse system produced better blastocyst formation rates, especially between 35 and 42 years old, lower embryo arrest rate and the ability to produce approximately 1 (one) extra blastocyst per cycle, which could increase the cumulative pregnancy rates.

Time-lapse incubation should be considered as an alternative to traditional incubation

Use of time-lapse to improve selection of euploid blastocysts was presented by Sundheimer et al (P-100). In this study, pregnancy rates of euploid embryos with a single thaw transfer created in the EmbryoScope time-lapse system were statistically significantly higher than with standard incubation (80.8% versus 67.3%, p<0.05). Combining patients with a single thaw cycle as well as an eSET transfer, the pregnancy rate in the Embryoscope was 79.7% versus 67.3% (p<0.05). The study concluded that given the significantly improved pregnancy rates, time-lapse incubation of embryos should be considered as an alternative to traditional incubation.

Prediction of euploidy

Development of a model using morphokinetic variables and morphology to predict which embryos were most likely to be euploid was shown by Desai et al. (P-109). For the morphokinetic variables, the difference from start of blastulation (tSB) to expanding blastocyst (tEB) showed that the odds ratio of euploidy decreased by 4.5% for each hour difference (p<0.002). In addition, embryos with a tSB of less than 96.2 hours were 1.5 times more likely to be euploid than slower embryos p=0.0005. Finally, embryos with more than 1 dysmorphia at the cleavage stage lowered the odds of being euploid by 49% (p=0.003).

Focus on genomics and preimplantation genetic testing for aneuploidy

Two 'hot' topics dominated the field of preimplantation genetic testing for aneuploidy (PGT-A) this year at ASRM. Sessions on mosaicism and non-invasive PGT (niPGT) generated a significant amount of interest with standing room only in the meeting rooms!

Mosaic embryo transfers can result in pregnancies and live births

Firstly, Viotti from the Zouves Foundation for Reproductive Medicine (0-78) presented data on the largest analysis of transferred mosaic embryos, combining data from several participating clinics. Clinical outcome data was collected from 372 transferred embryos classified as mosaic from PGT-A. Analysis of the data showed that mosaic embryo transfers can result in pregnancies and live births, although with decreased success compared to euploid embryos. Higher levels of mosaicism correlated with poor clinical outcomes and complex mosaics involving more than two chromosomes should be deprioritised. This large data set represents a valuable resource to generate guidelines on mosaicism for embryo transfer and prioritisation in the clinic.

This presentation on mosaicism was followed the day after by a session hosted by Dr Hickman from Houston IVF, Dr Katz-Jaffe from CCRM, Dr Large from Cooper Surgical and Ms Lauri Black from Pacific Reproductive Genetic Counselling developed in cooperation with SART, SBRT and PGTSIG (INT02). The session started with Dr Katz-Jaffe describing the background behind mosaicism, Dr Large providing examples of mosaic interpretation and Ms Black discussing her experience of how patients are counselled in the event that only mosaic embryos are available for transfer. The session was supplemented by audience members accessing an interactive audience response system and who were posed with a number of key questions; results were displayed on the screen in real-time adding to the dynamic nature of the session and thus generating debate.

While the debate continues, new data, discussions and the recently published guidelines from PGDIS help to support the community in determining the best approaches for interpretation and prioritising of embryos.

Non-invasive PGT

The second hot topic of the meeting was on non-invasive PGT (niPGT). Hosted by Dr Rechitsky from RGI, Dr Wells from IVI RMA and Dr Rubio from iGenomix and developed in cooperation with PGTSIG (INM06). The session aimed to inform the audience of the potential approaches to niPGT based on testing blastocoel fluid and spent culture media, in addition to discussing the expected diagnostic implications of niPGT. Dr Wells gave a comprehensive overview of the sample types used for PGT-A from the polar body, D3 to D5 biopsy and onto the opportunity for less invasive blastocoel fluid and non-invasive spent culture media. Rubio complemented this introduction with her own experience over a period of 4 years investigating whether a non-invasive approach for PGT-A is ready for clinical application.

A poster from Dr Kuznyetsov and colleagues from CreateIVF (P-337) who at ESHRE earlier this year presented data on combined spent embryo culture media and blastocoel fluid analysis presented data attempting to reduce the risk of maternal contamination, a risk factor for the success in niPGT analysis. The team utilising the VeriSeq PGS assay investigated removing the lysis step before amplification by SurePlex and found high concordance between lysis, no lysis and TE biopsy. Thus, removal of the lysis step prior to amplification could theoretically reduce the risk of maternal contamination.

Many groups in the field of PGT are investigating the source and mechanism of cell free embryonic DNA, the optimal conditions for sampling and the concordance to trophectoderm biopsy to determine whether this approach is a non-invasive alternative to an embryo biopsy.

Positive effect on pregnancy rate of extending the exposure time to EmbryoGlue with vitrified blastocysts

Dr Perez (O-273) presented in a late breaking session the positive effect on pregnancy rate of extending the exposure time to EmbryoGlue with vitrified blastocysts. Exposure of warmed blastocysts to EmbryoGlue for around 1.3 h, 2.2 h and 3.3 h resulted in a clinical pregnancy rate of 54 %, 68 % and 81 %, respectively. Data from an RCT on EmbryoGlue was also presented by Dr Kandari (O-113). Embryos from polycystic ovary syndrome patients were selected using time-lapse and then transferred in EmbryoGlue or culture medium. The implantation and live birth rates were significantly higher following transfer in EmbryoGlue. Listen to the below interview with Dr Perez at ASRM. 

Looking inside the cell

During the first plenary session Dr Plachta presented some beautiful and revealing fluorescent images, using various techniques to investigate the mechanisms that form the early mammalian embryo.

Using time-lapse microscopy Dr Otsuki (O-080) tracked refractile bodies to demonstrate that cells cleaving earlier in human embryos during the third and fourth cell divisions are more frequently allocated to the ICM. Dr Cecchino (O-081) compared the bioenergetic properties of granulosa cells from donor oocytes and those from infertile patients ≥ 38 years old. It was found that granulosa cells from the infertile patients had significantly lower mitochondrial respiration and glycolytic capacity. Dr Van Varenbergh (O-182) presented a matched control study that investigated the expression of 3 genes in the cumulus cell to generate a score for each oocyte. It was reported that the clinical pregnancy rate following day 3 transfer could be almost doubled. The possibility of using granulosa cells as a diagnostic tool continues. Dr Seli (O-183) investigated the predictive value of mitochondrial copy number on blastocyst viability. The study suggests that mtDNA copy number is not associated with sustained implantation and is not useful in selecting or ranking the embryo for transfer.

Cryopreservation of ovarian tissue

Dr Oktay chaired a session on the twenty years of progress in ovarian tissue cryopreservation. In the session on ovarian tissue cryopreservation. His overview of the work performed over the past two decades was followed by Drs Demeestere and Suzuki discussing the methods utilised. While vitrification is increasingly used, slow freezing remains the standard method for storage of ovarian tissue today.

News from China

The Chinese Society for Reproductive Medicine showed results from the 2017 Chinese registry. With around half of the clinics participating, 400,000 IVF, ICSI and FET cycles were included in the report. Compared to EU or USA, the average age of patients in China is significantly younger but a shift towards increasing age is expected. The society also had a session on in vitro maturation (IVM). Technical aspects and current knowledge were presented from leaders of 2 strategic programs on-going in China (Drs Liang and Fan). An IVM versus IVF patient RCT was presented by Dr Vuong (O-268). Using patients with high antral follicle count, the study could not show non-inferiority of the IVM method compared to the standard IVF patient group. The method, however, suggests an improvement on IVM techniques used so far.

More information

If you would like to read more about some of the research presented at ASRM you can download our selection of abstracts below.