IVF - In Vitro Fertilization

Genetic testing of embryos is not legal in every country. To understand the nuances by region, please see our global courses.

Clinics will often use two or three criteria to determine which embryo is best and should be transferred first. These include:

• How Fast The Embryo Is Dividing: How quickly an embryo reaches a specific stage of development (like blastocyst or cleavage stage).

• Morphological Grading: An embryologist’s interpretation of how specific regions of the embryo appear.

• Preimplantation Genetic Testing: Whether an outside laboratory believes the embryo has the appropriate number of chromosomes.

How Fast The Embryo Is Dividing

Most experts will tell you that the speed at which an embryo reaches any given stage (like the blastocyst stage) correlates with its odds of success. Below is data from over 1,000 transfers of frozen-thawed embryos with results broken out by the day the embryos reached the blastocyst stage. As you can see, embryos that reached the blastocyst stage in five days were more likely to lead to a birth. But, embryos that reach blastocyst in six days clearly have the potential to lead to births. For patients considering transferring cleavage stage embryos, the same holds true: the earlier the embryo reaches that stage, the more likely that it will lead to a birth.

As an aside, while embryos reaching blastocyst on Day 7 are less desirable than those reaching by Day 5 or Day 6, a small but growing body of evidence suggests Day 7 embryos can also lead to live births and should thus be frozen for use. Today, most clinics discard embryos that don’t reach the blastocyst stage by Day 6. We believe that may be a mistake.

An important note for patients undergoing genetic testing of their embryos: There is an increasing number of embryologists who prefer to allow embryos to grow an extra day past the initial blastocyst stage before performing the biopsy required for genetic testing. Since the biopsy involves removing several cells from the embryo, they may feel that the embryo is likely to sustain less damage if given an extra day to grow. That said, an embryo that is biopsied on day 6, but has reached blastocyst stage on day 5 may have the same or similar chances of success as any other embryo that reached blastocyst on day 5 and was frozen at that time. If you have been told you have an embryo that was frozen on day 6, it may be worth confirming with your clinic what day the embryo was considered to reach blastocyst, regardless of the day of biopsy & vitrification.

Grading On Morphology

Patients often have their their embryos graded on a scale that includes one number followed by two letters (like 4AB). This is called a morphological assessment. This combination of numbers and letters represent how “expanded” the embryo is, how many cells comprise the inner cell mass (which develops into the fetus) and the trophectoderm (which develops into the placenta).

While “expansion” is listed first, it’s not the most important grade. That distinction belongs to the grade for inner cell mass, or what will become the fetus. An analysis of over 500 embryos at the University of North Carolina revealed that grading of the inner cell mass is most correlated with an embryo’s odds of success.

A critical question is, taken together, how well do these three morphological scores correspond to the likelihood an embryo will lead to a live birth? That can be difficult to assess because weighing and lining up various grades within 3 differing criteria is subject to interpretation (for example, is a 3AA better than a 4AB?). However, most studies that have tried to do this come to two conclusions:

• An embryo that has better morphological traits is more likely to lead to a live birth than an embryo that has poorer morphological traits

• And yet, morphology is not predictive of whether an embryo will work; “great looking” embryos fail often and “less good looking” embryos are very capable of working

Below is an excellent analysis from Japan of over 1,500 embryos in which embryos are classified into six buckets by their morphological grades. As you can see, there’s a predictable downward slope and thus correlation between morphological grading and the odds an embryo leads to a live birth. Yet, the less attractive embryos can still lead to live births, especially for younger patients. In fact, the better-looking embryos from a woman over age 38 typically succeed as often as the less-good-looking embryos from a woman under 33.

As many experts will tell you, grading the inner cell mass and trophectoderm is subjective and some laboratories are tougher graders than others. That makes it hard to generalize how often an “AA,” “AB,” “BA,” “CC” (or what have you) embryo will lead to a live birth.

Pre-Implantation Genetic Testing (PGT-A)

As we’ve covered before, genetic testing of the embryos can be an effective method to rule out embryos unlikely to lead to a live birth. While there is evidence that chromosomally-abnormal (“aneuploid”) embryos have led to live births, it’s very uncommon. For that reason, embryos that are chromosomally-normal (“euploid”) should be the clear priority. However, the vast majority of patients do not have genetic testing of their embryos done and so this information is only available to those prepared to pay about $5,000 for the results.

As mentioned in the prior lesson, there’s very little data on transfers success rates with aneuploid embryos because patients seldom transfer aneuploid embryos. The odds that the top of our range (e.g. 10%) may well be high. Some doctors believe 0 - 5% would be more accurate, and still optimistic.