Does chromosomal screening of oocytes before embryo transfer improve live birth rate?

September 17, 2018

The largest randomized trial published to date examined whether chromosome screening of select embryos for transfer improves the likelihood of a live birth. Steve Ory, MD, a member of the Contemporary OB/GYN editorial board provides commentary on the findings.

Preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening of select embryos for transfer did not increase the likelihood of a live birth among women of advanced maternal age who underwent a single cycle of intracytoplasmic sperm injection (ICS) within 1 year, according to results of a multicenter randomized controlled trial (RCT) published in Human Reproduction.

The largest randomized trial published to date spanned nine centers in seven European countries and was led by Karen Sermon, MD, PhD, from the Research Group Reproduction and Genetics of the Vrije Universiteit Brussel (VUB) in Belgium.

The study enrolled 396 women aged 36 to 40 who were randomized to either PGT-A (205 subjects) or no PGT-A (a control group of 191 subjects).

After 1 year, both groups achieved a live birth rate of 24%.

“Given the limitations of the study, I am not surprised by the results,” said Steven Ory, MD, a reproductive endocrinologist in private practice in Margate, Florida and member of the Contemporary OB/GYNeditorial board. “Finding an embryo with 46 chromosomes by PGT-A is the holy grail for success with in vitro fertilization (IVF).”

Dr. Ory said failure to produce an embryo with 46 chromosomes is the most common reason for a failed IFV cycle. “Hence, any technology that helps us improve the odds of finding such an embryo is likely to have a huge positive impact on the outcome of an IFV cycle,” he said.

However, Dr. Ory said the study highlights the limitations of applying a complex, operator-dependent technology in multiple sites. “The study’s live birth rate of 24% in both groups is significantly below what many high-performing centers have reported with PGT-A,” he said.

PGT-A, previously known as preimplantation genetic screening (PGS), has been pursued over the past 20 years. “Initially, there was a lot of excitement over an earlier technology using fluorescent in situ hybridization (FISH) to help identify abnormal embryos,” said Dr. Ory board member. “But when the technique was rigorously tested in randomized controlled trials, it proved to be a failure.”

The current study used a newer technology-array comparative genomic hybridization (aCGH)-for chromosomal analysis, which is superior to FISH in overcoming some of the previous challenges of the older technique. “FISH did not test for all of the 46 chromosomes, it was conventionally performed on 3-day-old embryos (cleavage-stage embryos) andthe cells that were typically obtained did not necessarily represent the true genetic makeup of the embryo,” Dr. Ory said. 

Despite the study being well designed and the first RCT of its kind, Dr. Ory believes it is less representative of PGT-A as presently performed in the United States. A potentially more reliable chromosomal analysis technology, NxGen MDx, is typically performed on cells obtained from the trophectoderm, which represent both maternal and paternal contributions. “Therefore, it is hard to say whether the European results can be extrapolated to a broader experience,” Dr. Ory said.

Also, the investigators were unsuccessful in recruiting as many patients as they hoped. “Thus the study may have been underpowered,” Dr. Ory said.

As for the additional expense of performing PGT-A, “if it improves the likelihood of having a successful experience and not having to undergo multiple embryo transfers or multiple IVF cycles, then the true cost could potentially be less,” Dr. Ory said. “But this is an unresolved question.”