Going Beyond Looks: The Road to Single Embryo Transfers in IVF

Just 25 years ago, only one in 10 women undergoing fertility treatment went home with a baby. To be successful, a woman needed to accept the transfer of three or four embryos to her uterus, despite the increased risk of multiple pregnancy and associated neonatal and maternal complications.

Moreover, embryos were introduced in to the uterus at the two- to eight-cell stage. The single most important criteria for embryo selection was simply morphology at transfer, explains Nina Desai PhD, HCLD, who heads Cleveland Clinic’s IVF laboratory, located at Cleveland Clinic Beachwood.

Advances in clinical and laboratory protocols have since changed the overall landscape of IVF, with higher live birth rates and fewer embryos being transferred. And yet morphology has remained the predominant embryo selection criterion.

“In the last five years, two new technologies, namely time-lapse imaging and preimplantation genetic screening (PGS) have been adapted by clinics to get beyond ‘looks’ in embryo selection for transfer,” says Dr. Desai.

Time-lapse imaging and EmbryoScope

Cleveland Clinic introduced time-lapse imaging into its fertility practice in 2012. By 2014, all patients had the advantage of continuous undisturbed culture in the EmbryoScope, a meticulously engineered incubation chamber with sophisticated video capabilities for time-lapse imaging of embryos as they grow.

“The wealth of information from this technology has allowed the assessment of embryo implantation potential using cell-cycle kinetics and visualization of nuclear and cleavage anomalies,” Dr. Desai explains. “We routinely use this technology to identify high-potential embryos and transfer them singly to patients, ultimately helping achieve a healthy outcome for mother and child.”

Significant shift in IVF practice

Embryonic aneuploidy contributes significantly to failed implantation. PGS addresses this issue by selecting embryos based on chromosome status rather than morphology.

“This represents a significant shift in IVF practice, and most importantly, allows patients to elect to transfer a single euploid embryo with a high expectation of a positive outcome,” Dr. Desai says. “Pregnancy rates with transfer of a single euploid blastocyst range from 55 to 65 percent in our IVF program.” She notes, however, that PGS is quite expensive and very labor intensive and invasive, requiring excision of cells from the blastocyst using a laser.

Examining embryo selection methods

A new study from the Cleveland Clinic IVF laboratory looks at the correlation between embryo growth kinetics and chromosome status with an eye toward finding a less invasive method to select euploid embryos.

“Preliminary data do indeed indicate that morphokinetic data available from time-lapse imaging may enhance the likelihood of selecting chromosomally normal embryos,” Dr. Desai says. “This is an intriguing possibility and we hope to exploit such information to help our patients!”

On the policy front

“The adoption of a single embryo transfer policy is imperative for the health of our patients and their babies,” she states. “However, this demands not only optimization of culture technology, but also embryo selection /deselection techniques.”

Development of noninvasive screening methods to assess embryo viability and implantation potential is the newest challenge in IVF and imperative as we continue to encourage elective single-embryo transfers. Cleveland Clinic is committed to this goal and is using its expertise and cutting-edge technology to continue to advance in this area.

References:

1. Desai N, Ploskonka S, Goodman L, Attaran M, Goldberg JM, Austin C, et al. Delayed blastulation, multinucleation, and expansion grade are independently associated with live-birth rates in frozen blastocyst transfer cycles. Fertil Steril. 2016;106(6):1370-1378.
2. Desai N, Ploskonka S, Goodman LR, Austin C, Goldberg J, Falcone T. Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles. Reprod Biol Endocrinol. 2014;12:54.
3. Desai N, Rambhia P, Goldberg J. Is there an increase in aneuploidy rate with delayed blastulation, multinucleation or cleavage anomalies? Presented at the American Society of Reproductive Medicine meeting 2016, Salt Lake City, Utah.