Time-lapse imaging said to improve embryo selection

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.

LONDON – Time-lapse imaging can help select the best embryo for implantation during fertility treatment, according to Joseph Conaghan, Ph.D., of the Pacific Fertility Center in San Francisco.

"Improved embryo selection may increase pregnancy rates following IVF [in vitro fertilization] and allow more patients to elect for single-embryo transfer [SET]," he noted at the annual meeting of the European Society of Human Reproduction and Embryology.

In recent years, there has been a move toward elective SET during IVF, but the main stumbling block has been that it is difficult to identify the best embryo to transfer.

"Historically, we have not had good pregnancy rates with frozen embryos, and it is always hard to convince patients to transfer just one embryo if they think that their chance of pregnancy is lowered," Dr. Conaghan said.

Although there are several methods available to try to select the most viable embryos, the one that Dr. Conaghan has been involved in testing in particular is time-lapse imaging. "As an embryologist, I like this technology a lot," he said. "The camera is seeing what we see, and we understand the information that we are getting."

The technology is based on identifying very early kinetic markers of embryonic development (Fertil. Steril. 2013;99:1035-43). Data show that how, and the rate at which, cells initially divide to form four-celled embryos can predict how well the blastocyst will form and later survive. Indeed, the duration of the first cytokinesis, the time between an embryo becoming three from two cells, and four from three cells, are all important stages (Nat. Biotechnol. 2010;28:1115-21).

In a recent prospective, multicenter cohort study (Fertil. Steril. 2013 [doi:10.1016/j.fertnstert.2013.04.021]), Dr. Conaghan and his associates reported on the ability of a time-lapse imaging technology to help select embryos with good morphology versus embryologists’ usual screening assessment of embryo morphology at day 3.

The technology used in the study was the Eeva (Early Embryo Viability Assessment) system developed by Auxogyn. This is one of several systems currently available; another is the EmbryoScope produced by the Danish company Unisense FertiliTech. They use computer-aided tracking to visualize the dynamic development of multiple embryos simultaneously.

While the EmbyroScopeis a self-contained system that sits on the lab bench, Eevais a microscope system that fits inside a standard incubator and an electronic touch-screen pad fits on the outside to allow the embryologist to see images taken by the microscope at 5-minute intervals.

Discussing Eeva, Dr. Conaghan explained: "The computer tracks development and tells you when an embryo has a high/low probability of making a blastocyst." Embryos that have a low probability of forming a healthy blastocyst are flagged by a yellow square whereas embryos with a high or good probability of forming a healthy blastocyst are flagged by a green square.

Five IVF clinics in the United States participated in the study, recruiting 160 women between them. Three experienced embryologists assessed patient records and morphology at day 3 for 775 embryos that had been separately evaluated using the Eeva system. There was no blinding to the Eeva results as the aim was to see if the technology could improve prediction rates for embryos that would have the best chance of implantation and a successful pregnancy.

The additional use of the time-lapse imaging technology was found to significantly improve the embryologists’ ability to identify embryos that would reach the blastocyst stage. The specificity for using day 3 morphology alone was 41.9%, 59.7%, and 79.5% for each of the three embryologists respectively. When Eeva was added into the mix, the rates increased to a respective 84.0%, 86.3%, and 86.6%.

Importantly, the additional use of Eeva was able to help embryologists to identify "good morphology" embryos, Dr. Conaghan said. These are embryos that have divided to become six or more cells, with perfect symmetry and less than 10% fragmentation.

"It’s important to point out that if an embryo does get a low score that it doesn’t mean that it is going to fail, he said. "It means that there is a high probability that the embryo is [perhaps] going to fail, but it doesn’t mean that we’re going to throw it away."

The ongoing studies – EPIC(Eeva Pregnancy Investigational Clinical Study), MERGE (Registry Study of Traditional Morphology Grading Combined With Eeva in IVF Treatment), and CCS(Correlating Time-Lapse Parameters Detected by the Eeva System With Comprehensive Chromosome Screening Results) – are assessing the use of the time-lapse imaging system, looking at aneuploidy, fragmentation, and the prospective use of Eeva to assist in embryo selection for transfer.

"I think that this is a very exciting technology," Dr. Conaghan said. "It has the potential to eliminate embryos from transfer consideration."

During a separate session, Catherine Racowksy, Ph.D., of Brigham and Women’s Hospital in Boston, made some general comments on the use of time-lapse imaging for optimizing the selection of embryos for IVF. "Time-lapse imaging really does hold a great deal of promise," she said. It is a noninvasive approach, and several teams have shown that the kinetic time points being assessed can be replicated.

"The tracking algorithms derived from retrospective cohort imaging data show that there are these key early cell cycle parameters that have value in predicting blastocyst formation and the ploidy of the embryo," Dr. Racowsky commented.

Prospective, randomized trial data are critical before this technology hits routine practice. "We cannot have these machines in the lab, hoping that they are going to help us in predicting the development potential of embryos if we haven’t proven to ourselves that they really are better than just looking down a microscope at static time points," she concluded.

Dr. Conaghan and Dr. Racowsky reported having no relevant financial disclosures.