What Determines A Normal Embryo?

“My embryos were normal, but I didn’t get pregnant.” It’s one of the most common statements we hear from many of our patients who come to us for second or third opinions. How do we know the embryos created in an IVF cycle are normal before we transfer them to the uterus? The simple answer is, we really don’t. The likelihood an embryo will successfully implant is about 46% for women under age 35, according to national averages from over 400 IVF clinics in the U.S. For women within ages 38 to 40, those implantation chances drop to 28% and at ages 41 to 42, less than 18% of embryos will successfully implant. With increasing age, miscarriage rates also increase. There are three potential criteria that embryologists can use to assess embryo quality, and to help physician colleagues maximize IVF success:

Developmental

A fertilized egg starts as a one-cell entity that should start dividing within 24 hours, and by 48 hours reach the 4- to 10-cell stage (preferably 6 to 8 cells). Embryos are sometimes classified into stages based on their day of development, and the day-3 stage is when many centers in the U.S. transfer embryos to the uterus—often several at a time. These multiple transfers are a shotgun attempt to bring about pregnancy because it is virtually impossible to determine that any single day-3 embryo is normal. IVF labs with more advanced experience will follow day-3 embryos to the blastocyst stage, which ideally begins on day 5. Many embryos also become blastocysts on days 6 or 7, and there is good evidence that many of these blastocysts can also lead to normal pregnancies. The chance of a single day-5 blastocyst implanting successfully is much higher than a day-3 embryo. At our center, tools like the EmbryoScope can potentially aid our embryologists in selecting the best embryo for transfer. A combination incubator, microscope and time-lapse camera, the EmbryoScope takes images every 10 to 15 minutes, giving embryologists the full picture of an embryo’s development, rather than just snapshots at key points.

Genetic

Most day-3 embryos stop growing and don’t develop into blastocysts. Embryos that stop developing on day 3 or 4 are most likely abnormal (either genetically and/or metabolically), and will either not implant or can lead to miscarriage. Unfortunately, blastocysts often harbor chromosome abnormalities as well, and about 50% of blastocysts also have the wrong number of chromosomes. Our selection of a chromosomally-normal blastocyst by a technique called pre-implantation genetic screening (PGS) will reliably lead to embryo implantation 55% to 65% percent of the time. This has been published and presented at national meetings by several well-regarded IVF centers, including ours. Many IVF patients could benefit from PGS and subsequently require fewer treatment cycles.

Metabolic

This is the next frontier for determining embryo health, and may allow us to improve implantation significantly beyond 55% to 65%. Stay tuned on the topic of embryo diagnostics, and possibly even embryo therapeutics that will lead to better IVF success in the future. From a scientific perspective, we’re just scratching the surface in determining what defines a truly normal embryo.