Embryo Quality and Grading

Can we estimate results  of In Vitro Fertilization? What are the chances of a successful embryo transfer? What do embryo quality and grading mean? Do they tell anything about possible outcomes? These are the questions intended parents worry about the most. While embryo grading is a complex medical process, parents need and should be informed about every important step on their fertility journey.

 

What do Embryo Quality and Grading Mean?

 

Embryologists use embryo grading system in order to make predictions about embryo transfer results. These predictions do not depict the reality accurately. A lot of embryos with low or middle grading lead to successful pregnancies. Moreover, not all high quality graded embryos result in gestation. This happens mainly because grading does not give an information about embryo’s genetics.

Embryo grading system is still a powerful tool that gives a good impression about which embryos are appropriate for transferring / freezing. Estimating embryo’s quality and potential is an important step. It helps intended parents to save time, finances, protects from unexpected misfortune and may facilitate their parenthood journey.

There is no universal grading system. In some clinics grade 1 is better than 4, while in others 4 may indicate the best quality. The most common practice is to observe an embryo after 3 or 5 days of fertilization. However, embryos are not on the same development stage on these days. Embryologists use different grading systems for day 3 and day 5.

 

Grading on day 3

 

On the day 3, embryos are on their “cleavage stage”. This means that cells in the embryo (blastomeres) are dividing. Observation happens under a high power microscope. On the day 3 after retrieval, embryo itself is not growing in size – only the cells are being replicated.

Accordingly, grading criteria number one is the number of cells in the embryo. The desired number of cells on the day 3 is 6-10. Based on experience, embryos containing 6 to 10 blastomeres on day 3, are more likely to result in successful pregnancy.

Criteria number 2 is the presence of fragmentation. Fragmentation/Blebbing is the process when the inside of the cells break off and form fragments. These blebs do not contain nucleus. Nucleus is the cell storing cell’s genetic material, DNA. As fragments/blebs are separated from the nucleated part of the cell, they are not referred to as cells. It is preferable to have little or no fragmentation at all. On the other hand, embryologists may capture multinucleation (presence of more than one nucleus per cell). Multinucleation is very hard to identify but may unfortunately indicate chromosomal abnormality of the embryo.

Embryo quality and grading includes one more important criteria – cell regularity. It is desired that blastomeres are of the same or close to the same size.

After the observation on the day 3,  embryos having no fragmentations and including equally sized 6-10 cells will be considered of high quality and will be assigned the highest grade. Laboratory will assign further grades according to their own system. The higher the quality grades are, so is the likelihood of successful implantation.

 

Grading on day 5

 

On the 5th day after fertilization,embryo contains increased number of cells and a fluid cavity. As the cells are growing, they start to form in different types. We encounter two cell types on the day 5. First type forms the Inner Cell Mass (ICM) and the second one is called Trophectoderm Epithelium (TE). Day 5 embryo is referred to as Blastocyst and has reached the development stage when it is getting ready to attach itself to the uterine lining (Implantation).

ICM will grow into fetus and TE will form pregnancy essential tissues.  Due to their importance for gestation, day 5 grading system evaluates both cell types separately. ICM and TE will be both observed for their amount and density (how tightly are they packed). For example a lot of tightly packed cells indicate higher quality than loosely packed fewer ones.

Blastocyst should implant soon. Above mentioned cell types divide and fluid cavity has to enlarge and hatch out of its shell.  Fluid cavity’s volume in the embryo is one more criteria of 5th day grading.  It should begin to outgrow the space inside of the shell (zona pellucida) and then the blastocyst will be ready for the implantation.

Day 5 embryo will be assigned the higher quality grade, when fluid cavity has reached the appropriate volume, ICM is tightly packed, is sufficient in amount and TE is also forming a cohesive layer with sufficient quantity of cells.

As already mentioned, clinics may use different grading systems and utilize numbers or symbols to assign grades. However, most of the laboratories use exactly above mentioned criterias to evaluate the potential of an embryo.

While talking about the chances of successful gestation, high embryo quality and grading is not  a 100% guarantee. There are far more details included in the successful outcome. Sometimes an embryo does not implant because it has a genetic or chromosomal abnormality. It also happens that a lower grade embryo results in an unproblematic gestation because it has healthy genetics. A lot of clinics will suggest doing preimplantation genetic screening(PGS). This procedure checks chromosomal normality in the embryo.

Positive results in PGS and middle to high graded embryo already give a reasonable purpose to estimate a healthy pregnancy.

 

Reasons of Using an Egg Donor

How should parents know if it is time to start thinking about finding an egg donor? What if it is too early or what if donation is not needed at all? We will try to figure it out.

 

First of all, we have to mention that egg donation has become really successful. Procedures that use fresh embryo (! not frozen) have the likelihood of 43% to result in pregnancy.  A number of couples that want to expend their families have now the possibility to do so.

 

Situations vary. Females may experience fertility issues of several kinds. It is advisable to use an egg donor, when :

 

  • Follicle-stimulating hormone (FSH) level is high

In females, FSH helps to regulate menstrual cycle and produce eggs by ovaries.  Doctors measure the amount of the hormone in a blood sample. High level of FSH may mean the loss of ovarian function, menopause, polycystic ovary syndrome, chromosomal abnormality or the inability of the body to produce good quality eggs for fertilization.

 

  • Luteinizing hormone (LH) level is high

Similar to FSH, LH hormone regulates menstrual cycle and egg production. Doctors measure its amount in a blood or urine sample. Normally, levels of LH and FSH are rising and lowering simultaneously.  High levels of luteinizing hormone may also mean ovarian failure.

 

  • Anti-mullerian hormone (AMH) level is low

AMH is a substance produced by egg sacs, containing immature eggs. Blood test will reflect the remaining egg supply of a female. If the hormone level is low, the ovarian reserve is low accordingly.

 

  • Polycystic ovary syndrome (PCOS)

PCOS is a condition when female hormones are out of balance. We have already discussed this issue and you can read more about polycystic ovary syndrome on our blog.

 

  • Females are over 40

As we have already mentioned several times, age plays one of the major roles in infertility. Females in their 40s usually have high FSH and LH hormone levels, as well as low AMH level. With age, body’s reproductive system is becoming less functional. Females over 43 years tend to use egg donors for better outcomes. Ageing of Europe is also a demographic phenomenon and is characterised by a decrease in fertility. Many couples avoid creating/expanding families until they are 40. Consequently, their chances of reproduction without assistance are decreasing significantly. Same applies for the USA.

 

  • Females have menopause

Menopause is a normal, biological process for females in their 40s or 50s. However, it stops menstrual period permanently and so does it end fertility.

 

  • Mother may transmit a genetic disease

Many couples prefer to use an egg donor in order to prevent transmitting genetic disease to a child.

 

  • Several IVF attempts have failed

As we already said, in vitro fertilization is a process of fertilizing egg with sperm outside the body, in a laboratory dish. After couples have experienced 4 unsuccessful IVF attempts and doctors think the egg quality is poor, then it’s better to consider finding a donor.

 

Egg donation is used widely by LGBT couples. Same sex male couples from all around the world as using the donation  procedure to expend their families and become parents.

 

If couples experience above mentioned issues and doctors have already advised to think about donation, then they got a reasonable motive to do so. However, with the right agency and professionals, there is nothing to worry about 🙂