Study Looks at Culture Media and Kinetics of Embryo Development to Refine Embryo Selection

At Cleveland Clinic’s Fertility Center, embryos are grown in a special incubator called the EmbryoScope that contains a time-lapse video camera, giving a continuous record of embryo development.

This sophisticated imaging technology has allowed Cleveland Clinic’s In Vitro Fertilization (IVF) Laboratory to detect abnormal behavior in developing embryos that previously was missed. This, along with observations on the kinetics of embryo growth, makes it easier to identify the embryo most likely to be viable. Such information reduces the need to transfer several embryos at the same time to a patient’s uterus — often done in the expectation that at least one will implant — which can result in a multiple pregnancy that puts the mother and babies’ health at higher risk.

Nina Desai, PhD, HCLD, Director of the IVF Laboratory, and her staff are still refining the center’s efforts, looking for new techniques to determine which embryo is the best choice. Dr. Desai recently conducted a study looking at whether a particular type of culture media might affect morphokinetics, embryo dysmorphism and euploid rate. She presented the data at the 2017 American Society for Reproductive Medicine (ASRM) Scientific Congress & Expo.

“So much of the research in my lab involves studying the kinetics of embryo development under different conditions,” she says, “and trying to correlate these factors to ‘good’ embryos most likely to implant or to be chromosomally normal and those with less potential.”

Measuring development, applying an algorithm

For her study, Dr. Desai took a total of 729 zygotes from 68 consecutive patients undergoing IVF/intracytoplasmic sperm injection (ICSI) with preimplantation genetic screening (PGS). The normally fertilized zygotes were then cultured in either G-TL medium or Global medium with 10 percent serum protein supplement (SPS).

Dr. Desai assessed the embryo growth and annotated developmental endpoints such as compaction, morula formation, timing of start of blastulation and blastocyst expansion. She also compared transfer results and euploidy rates between media and noted incidences of dysmorphisms — multinucleation (MU), reverse cleavage (RC) and direct uneven cleavage (DUC).

In addition, she applied an algorithm known as the aneuploidy risk classification scheme that calls for stratifying embryos into low- and high-risk groups according to tSB (start of blastulation) and tBL (time of blastulation). Timings were: Low-risk classification is tSB <96.2, tBL <122 hrs and high-risk is tSB>=96.2 tBL>=122 hrs.

Further testing

Dr. Desai’s analysis showed there was no difference between the two culture media when it came to embryo development and the percentage of normal embryos. However, she says, after biopsying each embryo to determine its euploid rate, she found that the algorithm worked for embryos cultured in the G-TL medium. As expected, the low-risk group had the highest number of normal embryos, the moderate-risk had the next highest and the high-risk had the lowest. But the embryos cultured in the GB medium did not fit this pattern. The moderate-risk group had a higher euploid risk than the high-risk group. “The algorithm needs some further testing with a larger data set,” Dr. Desai says.

For the moment, she adds, “I would say the selection of chromosomally normal embryos just using kinetics doesn’t yet have the precision we need, but maybe it can be used to enhance selection…even if you just get a 5 percent edge on being able to pick the right embryo, that is a help.”