Time-lapse photography and ART

March 1, 2014

Time-lapse photography applied to embryo development is commonly called morphokinetics, because it combines the morphological criteria that are typically used for embryo grading/evaluation with the kinetics of development for each embryo at certain predefined checkpoints.

 

In 2011, 163,039 assisted reproductive technology (ART) cycles were performed in the United States, resulting in 47,818 live births and 61,610 live-born infants, according to the Centers for Disease Control and Prevention (CDC) 2011 Assisted Reproductive Technology Fertility Clinic Success Rates Report.1 Nearly 70% of the ART cycles thus did not result in a live birth, underscoring how difficult it is to select the right embryo.

With demand for ART increasing, clinics will continue to feel financial pressure to improve the efficacy and efficiency of ART cycles. In a recent article by Chambers et al, the authors point out that “there are striking international differences in utilization of ART and embryo transfer (ET) practices, even among developed countries where the prevalence and causes of infertility are similar. The reasons for such disparities are multifactorial, and include the diversity of regulatory and funding environments, demographic differences, and the influence of sociocultural norms.”2

Despite more than 30 years of research and an array of scientific innovations, we have yet to find the proverbial “Holy Grail” of IVF success: A way to definitively identify developmentally normal embryos. If clinicians/embryologists were able to pick the absolute “best” embryos, then elective single embryo transfer (eSET) would be the standard of care, decreasing the number of multifetal pregnancies and resultant complications. In fact, according to the CDC data cited above, multifetal pregnancies are a common occurrence.

An old technology is ‘new’ again

Now new hope for identifying normal embryos is coming from an old technology: time-lapse photography. Around since the early 20th century, time-lapse photography was first used by scientists who took continuous sequential photographs of plants and played back the images at a fast speed so that hours or days of change could be appreciated in a matter of seconds. We have all seen time-lapse images of flowers blooming, clouds moving, or even people going about their daily lives. What is miraculous about these short clips is that when they are played at normal speeds, time appears to be elapsing more quickly, allowing subtle changes to be identified and studied.

Time-lapse photography applied to embryo development is commonly called morphokinetics because it combines the morphological criteria that are typically used for embryo grading/evaluation with the kinetics of development for each embryo at certain predefined checkpoints.

Morphokinetics eliminates the need for an embryologist to take an embryo out of an incubator at set intervals and evaluate its development under a microscope. Instead, the embryo remains in a chamber, where images are continuously recorded and evaluated remotely.

What piques our interest about time-lapse photography is the completely noninvasive nature of the technology. Time-lapse photography requires only a modified incubator system, an embryo, a camera, and a computer to process the images. Coupled with the many advances in ART labs in the past decade-such as improvements in embryo culture that allow embryos to grow longer and more robust, innovations in embryo biopsy techniques allowing clinicians to get better samples of genetic material, and the myriad other new technologies for enhanced genetic evaluation of an embryo-time-lapse photography could be a game-changer.

Two companies currently manufacture time-lapse technology for embryo evaluation: Auxogyn and Unisense FertiliTech. Auxogyn’s product is the noninvasive Early Embryo Viability Assessment (Eeva) System. Unisense FertiliTech’s product is the EmbryoScope. Both technologies allow for simultaneous imaging of multiple embryos and remote access to data/images.

 

 

Improving success rates through continuous incubation

What makes this technology a game-changer is that it allows embryos to develop in an undisturbed environment while giving the embryologist better ability to assess them. In conventional IVF labs, embryos are evaluated daily, but removing them from the incubator interrupts incubation (Figure). With continuous time-lapse monitoring systems, embryos are continuously incubated, often until the day of transfer. This limits temperature variations and the potential effects of environmental exposures, movement, and trauma.

Although these factors may not all be crucial for proper embryo development, maintaining a continuous temperature does seem to mimic the normal physiology of the human reproductive tract.

This may explain why time-lapse photography appears to be improving ART success rates so dramatically. A 2012 retrospective analysis indicated that culture and selection of embryos with time-lapse monitoring significantly improved the relative probability of clinical pregnancy (+20.1% per oocyte retrieval, +15.7% per embryo transfer).3

Data derived from the developmental imaging have become invaluable for other reasons. Chromosomally normal and abnormal embryos have been noted to have different kinetic behavior.4 Data on “normal” embryo behavior, however, are still being amassed, so these studies should be read with caution. Before we can call something abnormal, we need to make sure we know what is normal.

A new culture of embryology

The last aspect of time-lapse technology that really excites us is the potential for performing embryologic assessment remotely. Images could be processed, scored, and evaluated by computers, to assist in ultimately selecting the best embryo for replacement. Patients in regions where resources are scarce, such as the developing world, could have access to world-class embryologic assessment.

A senior or supervising embryologist could oversee images from clinics around the world and offer guidance, teaching, and insight remotely. In fact, the products offered by both of the companies mentioned above have tablet-compliant features.

It is incredible to think that a photographic method that is more than 110 years old is now the state of the ART today.


 

References

1. Centers for Disease Control and Prevention. 2011 Assisted Reproductive Technology Fertility Clinic Success Rates Report. http://www.cdc.gov/art/ART2011/index.htm. Accessed February 10, 2014.

2. Chambers GM, Adamson GD, Eijkemans MJ. Acceptable cost for the patient and society. Fertil Steril. 2013;100(2):319–327.

3. Meseguer M, Rubio I, Cruz M, Basile N, Marcos J, Requena A. Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study. Fertil Steril. 2012;98(6):1481–1489.

4. Basile N, Nogales MD, Bronet F, et al. Increasing the probability of selecting chromosomally normal embryos by time-lapse morphokinetics analysis. Fertil Steril. 2014;101(3):699–704.

 

Dr. Levine is Clinical Fellow, Reproductive Endocrinology & Infertility, Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York.

Dr. Goldschlag is Assistant Professor of Clinical Obstetrics and Gynecology and Assistant Professor of Clinical Reproductive Medicine, Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York.