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A Guide to Predicting an Embryo’s Success Rate

Success rates are a popular topic in the fertility world. After investing so much time, money, and effort into assisted reproductive technologies (e.g. in vitro fertilization), people are eager to know their chances of success at each step of the process. Your doctor should be able to provide you with estimated success rates, and these estimated rates can also be calculated online with tools such as the CDC’s IVF Success Estimator. Keep in mind, though, that these are all estimates, and multiple factors must be considered when calculating your success rates.

While estimating the success rate of an embryo transfer (the transfer of an embryo(s) from a culture dish in an IVF lab to a uterus), there are two primary factors to consider: the embryo itself and the uterine environment. This guide will explain how specific components of an embryo affect its chances of implanting and resulting in a healthy live birth.

All About IVF

Before an embryo is transferred to a uterus, it is created in a lab via in vitro fertilization (IVF). In short, eggs (oocytes) are retrieved from a woman’s ovaries and inseminated to achieve fertilization. If fertilization occurs, the resulting embryo(s) develop in a culture dish in the lab for up to 7 days (depending on each clinic’s protocol). Embryos that properly develop can be transferred to a uterus, biopsied for preimplantation genetic testing (PGT, see below), and/or frozen (cryopreserved) for future use. Embryos must meet specific criteria in order to qualify for any or all of these outcomes. Embryos that do not meet these criteria are deemed “unsuitable for transfer” and are typically discarded. Keep in mind that each clinic has its own qualifications, standards, and protocols.

About Embryo Development

An embryo’s rate of development is one factor that helps predict if an embryo is suitable for transfer. For example, an embryo that does not show signs of developmental progression is deemed “arrested in development” and should not be transferred. 
Embryos follow a timeline of developmental milestones both in vivo (in the body) and in vitro (in the lab), and, while they can result in healthy live births, embryos that develop at an abnormal rate tend to have lower overall success rates. This chart shows the “normal” developmental timeline for embryos as the cells inside them rapidly divide.

Days After InseminationNormal Stage of DevelopmentDescription
11 cellFertilized egg (zygote)
22-4 cellsCells begin to divide via mitosis
36-12+ cells,Early morulaIndividual cells begin to form a clump of cells known as an early morula
4MorulaThe early morula condenses to form a morula
Early BlastocystA small cavity (blastocoel) begins to form in the morula. The cavity takes up <50% of the embryo
BlastocystThe cavity begins to take up >50% of the embryo
5Full BlastocystThe cavity takes up 100% of the embryo
Expanded BlastocystThe embryo grows in size as the cavity expands. The shell (zona pellucida) around the embryo begins to thin out
6/7Hatching BlastocystA hole is created in the zona pellucida and the embryo begins to hatch from this hole
Hatched BlastocystThe embryo hatches from its shell in order to implant into the uterine lining

Embryo Morphology (Grade)

However, even embryos that reach these developmental milestones may not be suitable for transfer. Another factor that helps to predict an embryo’s success rate is its morphology, also known as its appearance or grade. Depending on the age of the embryo, grading can consist of any or all of the following factors:

  • 3 days after insemination (day 3, or cleavage-stage, embryos):
    • Number of cells
    • Amount of fragmentation
    • Symmetry between the cells
    • Abnormalities
  • 5/6/7 days after insemination (day 5/6/7, or blastocyst-stage, embryos):
    • Stage of development
    • Appearance of ICM
    • Appearance of TE

Day 3 embryos should ideally consist of 8 or more perfectly or moderately symmetrical cells and less than 20% fragmentation. These embryos should also not display any abnormalities, such as degeneration or the presence of large vacuoles. Remember that an embryo’s appearance does not guarantee that it will result in a healthy live birth since it is only one factor to consider when calculating an embryo’s overall success rate. However, embryos that are abnormal in development and appearance tend to have lower success rates.

Some clinics perform day 3 embryo transfers, while others prefer to wait until at least day 5. This website provides a detailed list of the pros and cons of day 3 versus day 5 embryo transfers.  Keep in mind that day 3 embryo transfers tend to yield lower overall success rates when compared to day 5 transfers. Embryo transfers can also be fresh (the embryo is not frozen beforehand) or frozen (the embryo is frozen beforehand). This website describes the advantages and disadvantages of fresh versus frozen transfers.

Once an embryo reaches the blastocyst stage of development, a different embryo grading system is utilized. This grading system records the embryo’s stage of development (see chart above) and appearances of its inner cell mass and trophectoderm. An embryo’s stage of development is often recorded as a number (using the Gardner scale) or letter(s) and begins once the embryo reaches the early blastocyst stage (this may vary between clinics). The inner cell mass refers to a cluster of cells in the embryo that eventually develops into the baby. It is typically graded using an A, B, C scale, with A as the highest grade. The trophectoderm refers to the cells that line the shell of the embryo and eventually develop into the placenta. These cells are also graded on an A, B, C scale, with A as the highest grade. Keep in mind, though, that embryo grading is subjective and may differ between embryologists. This chart contains more detailed information about the embryo grading system.

An embryo’s morphology can affect its success rate. As this chart from Natalist explains, embryos with higher grades result in higher pregnancy and live birth rates:

This chart does not provide data for early blastocysts and blastocysts since these embryos are often not transferred, biopsied, and/or frozen. Instead, these embryos are given another day or two to develop. If they develop, then they can be transferred, biopsied, and/or frozen. If they do not develop, they are typically discarded. One important note about this chart is that, even with a “perfect” looking embryo, there is still only a 50% live birth rate per embryo.

Embryonic Genetics

Another important factor to consider when calculating an embryo’s success rate is its genetic makeup. The primary method to detect genetic abnormalities in an embryo is preimplantation genetic testing (PGT).

PGT usually occurs when the embryo has reached the expanded blastocyst stage (this may differ between clinics) 5+ days after insemination. The process involves removing 5-10 cells from the embryo’s trophectoderm and sending those cells to a genetic testing lab. The embryo is frozen at the IVF clinic and stored there. The genetic testing lab then amplifies (makes many copies of) each cell’s DNA in the biopsy sample and a machine analyzes all of the DNA.

There are three types of PGT that can be performed, but the most common is PGT-A (aneuploidy). PGT-A determines what percentage of cells in the biopsy sample have the correct number of chromosomes. In short, each cell in the human body (except mature sperm and egg cells) contains two sets of 23 chromosomes (one set from the sperm and one from the egg). In some situations, an embryo may have a high percentage of cells with the wrong number of chromosomes. A common example of this is Down Syndrome, in which case the cells have an extra 21st chromosome. Since a woman’s egg quality and quantity decline as she ages, there tends to be a decline in the number of genetically normal embryos once a woman reaches 36 years of age. In these situations, PGT-A is often recommended to prevent the transfer of a genetically abnormal embryo.

The percentage of cells with an abnormal number of chromosomes in the biopsy sample determines if the embryo is considered genetically normal (euploid), abnormal (aneuploid), or mosaic (both normal and abnormal). While euploid embryos have few abnormal cells and high success rates, aneuploid embryos have many abnormal cells and low success rates. In particular, aneuploid embryos have low implantation rates, high miscarriage rates, and low live birth rates.

Mosaic embryos are a bit more complex since they contain both normal and abnormal cell lines. New studies have found that embryos with low mosaicism (their results lean more toward euploid than aneuploid) can often lead to healthy live births, though mosaic embryos do have lower overall success rates when compared to euploid embryos. The specific abnormality is also important because some chromosomal abnormalities can be lethal, while others may be harmless. For these reasons, it is always recommended that you speak with a genetic counselor prior to transferring a mosaic embryo.

There are two other types of PGT that are utilized as indicated: PGT-M (monogenic) and PGT-SR (structural rearrangement). These tests determine if any or all of the cells in a biopsy sample contain single-gene mutations (e.g. if the embryo is affected by or a carrier of the genetic mutation which causes cystic fibrosis) or structural rearrangements (e.g. a translocation or inversion). However, these tests are only performed when an embryo is at-risk of being affected with these conditions. Embryos that are affected are typically not recommended for transfer, but this should be determined by a licensed professional such as a genetic counselor.

Finally, an embryo’s grade does still matter even if an embryo is genetically normal. One study found that “excellent” quality euploid embryos (3AA, 4AA, 5AA, 6AA) had an 84.2% ongoing pregnancy rate, while “poor” quality euploid embryos (1BC, 2BC, 3BC, 4BC, 5BC, 6BC, 1CB, 2CB, 3CB, 4CB, 5CB, 6CB, 1CC, 2CC, 3CC, 4CC, 5CC, 6CC, 1BB, and 2BB) had an 35.8% ongoing pregnancy rate.

One Other Component to Consider

One embryonic component that tends to get overlooked is the embryo’s mitochondrial function. These structures inside of the embryo (which are originally from the egg) provide the embryo with the energy it requires to develop and function properly. According to this study, abnormalities in mitochondrial function can affect embryo development and implantation. Unfortunately, the only current methods for testing an embryo’s mitochondrial function are experimental (e.g. an embryo’s MitoScore value) and there is no way to determine an embryo’s mitochondrial function simply by looking at the embryo. However, it is worth mentioning that a woman’s mitochondrial function, like her egg quality and quantity, tends to decline with age.

Putting it All Together

This guide contains a lot of information about how an embryo’s components can help to predict its success rate. These components include the embryo’s developmental rate, appearance (morphology), genetic composition, and mitochondrial function. Abnormalities in these components can often affect an embryo’s chances of implanting and resulting in a healthy live birth. However, the embryo is only one key player in an embryo transfer. The uterine environment can also affect the success of an embryo transfer. Hopefully this guide will help you choose the best embryo to transfer for the highest chance of success.

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