Time-Lapse Images of Embryo Cell Division Are Giving IVF Researchers New Clues

Traditionally, clinicians have monitored IVF embryo cultures by removing embryos from incubators to check for cell division under a microscope. This is done just once a day to avoid compromising the health of the embryos.

With the EmbryoScope, a specialized culture incubator that contains a time-lapse video camera, scientists have a continuous record of embryo development without ever having to remove embryos from an incubator. This new technology is giving Cleveland Clinic’s IVF laboratory and clinicians greater insight into the kinetic and morphology patterns of individual embryos.

“There’s a lot of information to be gleaned by looking the time-lapse images,” says Nina Desai, PhD, HCLD, of Cleveland Clinic’s Fertility Center. “We’re seeing things we’ve never seen before.”

Dr. Desai and her colleagues recently performed two investigations using those time-lapse video images to look at how embryo cell division rhythms and characteristics might affect embryo chromosomal integrity. One study focused solely on multinucleated embryos (MU) while the other focused on MU, plus embryos with delayed blastulation and cleavage anomalies.

Dr. Desai and Linnea Goodman, MD, presented the research at the American Society for Reproductive Medicine 2016 Scientific Congress & Expo in Salt Lake City, Utah.

Are MU embryos more chromosomally compromised?

For the first study, the researchers recruited nine couples who had at least 20 percent of their embryos exhibiting evidence of MU on day two of continuous time-lapse culture in the EmbryoScope.

A total of 133 embryos were evaluated for chromosomal status. Of those, 54.1 percent, (72 out of 133), developed to the expanded blastocyst stage and were able to undergo trophectoderm (TE) biopsy on day five or six for genetic screening. Unbiopsied early blastocysts, as well as embryos arrested at cleavage/morula stage, were also sent for analysis.

Earlier studies have shown that MU embryos are less likely to implant in the uterus. The researchers had hypothesized that lack of implantation might be due to greater aneuploidy in MU embryos compared to non-MU embryos. The data, however, showed no difference in aneuploidy rate between MU and non-MU embryos (44.4 vs. 47.1 percent; P = 0.83). “We went into the study thinking there would be a relationship between MU and aneuploidy,” Dr. Desai says, “but that wasn’t the case.”

On the other hand, she says discovering that MU embryos are no more likely to be aneuploidy than non-MU embryos could prove helpful to some would-be parents. Typically, clinicians don’t opt to transfer MU embryos due to potentially lower implantation rates. However, Dr. Desai says, if a couple had only a few embryos to choose from and all were MU then at least there’s a good chance those embryos might still be chromosomally normal.

Delayed blastulation results in greater aneuploidy rate

For the second study, the researchers recruited 51 patients and cultured a total of 853 zygotes in the EmbryoScope. Using time-lapse images, they looked at embryo growth kinetics such as time to specific cell stages. They also performed TE biopsy on expanded blastocysts on either day five or six of culture.

Finally, preimplantation genetic screening (PGS) was performed on the embryos to evaluate the effect of cleavage anomalies, MU, cell kinetics and delayed blastulation on the chromosomal status of the embryos. “In the past, we never did as much chromosomal analysis,” Dr. Desai says. “Now PGS is all the rage.”

The researchers found the overall rate of MU, reverse cleavage and direct uneven cleavage was 31, 15 and 7 percent respectively. They obtained PGS results for 292 biopsied blastocysts and 40 percent were diagnosed as euploid.

Among the biopsied blastocysts, 109 were MU. As with the other study, the euploid rate was not significantly different between MU and non-MU blastocysts, 37 percent versus 43 percent. With reverse cleavage, only 27 percent of blastocysts (7 out of 26) were euploid compared with 42 percent of non-RC blastocysts (111 out of 265). This difference was not, however, statistically significant.

A significantly higher rate of aneuploidy was, however, associated with delayed blastocyst formation. Embryos taking more than 116 hours to form an expanded blastocyst had a 70 percent aneuploidy rate as compared to only 54 percent in rapidly dividing embryos forming expanded blastocysts in less than 116 hours.

Desai says they would like to repeat the studies with larger sample sizes. “This was an observational study,” she says, “our first look at things that might be important. Clearly, we see a need for more numbers.”