The numbers game: Why the number of eggs does not always equal the number of embryos
In mathematics, 1 + 1 always equals 2. Most patients assume, much like math, that our bodies function as an exact science and that taking medication will result in predictable results. As patients go through the IVF process, one of their big questions is, “How many eggs and embryos will I produce?”
During the stimulation process, doctors and patients alike focus on the number of developing follicles, often increasing or decreasing the dosage of medication to get the target number of follicles to develop. In the waiting room, patients will often compare notes, seeing whether they have more “eggs” developing and how they are stimulating compared to the person next to them! This numbers game can be stressful, and patients often expect the number of follicles to always equal the number of eggs retrieved and embryos produced.
The human body, however, is not a simple mathematical machine, and things do not necessarily add up exactly in the way we learned math growing up! Here are some insights into the numbers game of IVF.
Follicles versus eggs
Every other day or so during IVF stimulation, the doctor or ultrasound tech will diligently measure your follicles (the fluid-filled sacs that contain the eggs or oocytes) and will watch as they grow with fertility medication. People often assume that every follicle has an egg growing inside. However, one follicle does not always equal one egg retrieved.
Typically, only follicles that are 15 to 16 millimetres or more in size have a chance to yield a mature, viable egg. Also, at the time of egg retrieval, when these larger follicles are drained of fluid, not every one necessarily contains an egg. This is one of the reasons why IVF medications are used to stimulate more than one follicle to grow, so that even if some follicles do not contain eggs, you will still have some retrieved.
For example, having 15 follicles by the end of your stimulation does not always mean that 15 eggs will be retrieved. There could be more or fewer. As fertility doctors, we target 8 to 15 developing follicles and eggs retrieved in young patients with normal ovarian reserves, but this could be fewer or occasionally more, depending on each patient’s case and clinical picture.
The bottom line is, don’t obsess over your follicle count. Your doctor will tell you whether the stimulation is going well, and, ultimately, you will know the number of eggs retrieved on the day of the egg retrieval, but don’t be surprised if the numbers do not add up. Nonetheless, if you are stimulating and making multiple follicles, things are likely going reasonably well.
Eggs versus embryos
Once you’ve had your egg retrieval procedure and know the number of eggs that have been retrieved, the focus becomes how many embryos will result.
On the day after the egg retrieval, you will get a call about the number of fertilized embryos. Will these numbers always add up? Typically, no. Usually out of the eggs retrieved, we expect 60 to 80% to be mature eggs, and from those, 60 to 80% will fertilize to produce early embryos.
Why is this? Well, we are all human, and humans are error-prone. Not all of the eggs we produce are mature and viable; therefore, some will not fertilize or be able to be fertilized to produce embryos. This is all a part of a normal selection process. So, it is not unusual to have 13 eggs retrieved, 10 mature, and 8 fertilized embryos. The proportion of mature eggs and the fertilization rate will vary according to the individual and the couple.
Hooray! You have fertilized embryos! But things are just getting started. Nowadays, with the embryology lab being a great environment for the culture and development of embryos, we typically wait till day 5 (occasionally day 3) after egg retrieval to either transfer embryos or freeze them. Sometimes your doctor will want to do genetic testing on the embryos and freeze them prior to transferring in the next menstrual cycle. Usually, the fertility clinic will update you on how the embryos are doing on day 3 and on day 5 or 6.
Again, patients ask if the number of fertilized embryos = day 3 embryos = day 5 embryos? Typically, no. Natural selection, much like what happens in the body when we are trying to conceive naturally, also happens in the lab. Not all embryos are made equal, and the ones that are not viable will often stop growing over 3 to 5 days after the egg retrieval.
Usually, the embryologist will look for the cells in the embryo to approximately double their number every two days. So, by day 2 after retrieval, they should be at the 2 to 4 cell stage; by day 3, at 6 to 10 cells; and by day 5, up to a few hundred cells.
Patients often worry when some of their embryos don’t “make it” to day 3 or day 5. However, these embryos likely either were genetically abnormal or would not have continued to grow in your body either. This is nature’s way of selecting for the embryos that are of the highest quality and that have the best chance of producing a pregnancy. We usually see anywhere from a 20 to 50% blastocyst development rate (of day 5 embryos), depending on the patient’s age and infertility diagnosis.
All of this is to say that the goal of IVF and the extended culture in the laboratory, plus possible genetic testing, is to achieve a healthy viable pregnancy. So, rest assured that the ones that “make it” in the end are usually the ones with the best chance of achieving a pregnancy and a live birth. Quality is often better than quantity!