Does it seem like IVF is all a numbers game?

It can be quite frustrating for patients when their expectations in an IVF cycle aren’t met when it comes to the numbers of eggs and embryos. Why doesn’t the number of follicles equal the number of eggs retrieved? Why don’t all the eggs become embryos? Why don’t all embryos become babies? It seems like all a numbers game!

Most patients assume that our bodies function as an exact science and that an IVF cycle will play out in predictable results. As patients go through IVF, two of the most common questions are, “How many eggs and embryos will I produce?” and “If transferring one embryo is a 50% chance, then if we transfer two, won’t that be 100%?”

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. 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! This often means having to re-adjust a couple’s expectations to a more realistic scenario. With that in mind, here are some insights and expectations into the numbers game of IVF. These can help give you an idea of what to expect from your IVF cycle by employing a general rule of thumb based upon average results seen across all IVF clinics.

Follicles vs. eggs

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 number of eggs do not add up to how many follicles you had.

Our expectation: We expect to retrieve eggs from 80% of the follicles over 16 mm.

Eggs vs. mature eggs that can be fertilized

Once you’ve had your egg retrieval procedure and know the number of eggs that have been retrieved, the focus becomes on how many of these eggs are mature. Not all eggs will be mature. A mature egg has the right number of chromosomes for fertilization to occur, while an immature egg does not. So, we can only fertilize a mature egg. Our goal is the maximum number of MATURE eggs.

Our expectation: We expect 80% of the eggs to be mature.

Mature eggs vs. fertilized egg

At fertilization, the DNA from the sperm has to join perfectly with the DNA of the egg. But this doesn’t always happen. Why is this? Well, we are all human, and humans are error-prone. Sometimes, the DNA is imperfect in either the egg or the sperm and fertilization won’t happen. Other times, even if both the egg and sperm have perfect DNA, when they combine it does so in a faulty way so that chromosomes don’t line up as they should. This is all a part of a normal, biological selection process.

Our expectation: We expect 80% of the mature eggs to fertilize.

Fertilized egg vs. blastocyst

On the day after the egg retrieval, you will get a call about the number of fertilized eggs. Then the waiting game continues. It is completely natural for many of these embryos to stop developing, often known as embryo arrest. We provide the embryos the best environment to grow but not all will develop into a blastocyst, the final stage of embryo development, right before implantation. This is the stage when we will perform PGT (genetic testing). It usually occurs 5-7 days after retrieval.

Patients often worry when some of their embryos don’t “make it” to day 3 or day 5. However, these embryos were likely either genetically abnormal or would not have continued to grow in your body. 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.

Our expectation: We expect at least 40% of fertilized eggs will make it to blastocyst stage.

Blastocyst vs. euploid blastocyst

This is the final hurdle in getting the best embryo. Just because an embryo has developed and looks perfect under a microscope, the genetic makeup could still be abnormal. Doing preimplantation genetic testing, PGT, allows us to know if the embryo euploid. Euploid means it has the correct number of chromosomes, and the best chance to make a baby.

Our expectation: In embryos created from women with normal ovarian reserve and under age 35, we expect 60-70% of her embryos to be euploid, or normal. This is lower in women with low egg reserve and who are over 35 years old.

Live birth per embryo transfer

Phew! We’ve gotten this far, but it still feels like a numbers game! The most important question to ask at this stage is “What is the chance of a baby each time we transfer an embryo?” The fuzzy answer is that successful embryo implantation is a very intricate and complicated process. And the bottom line is that an euploid embryo has a better chance.

Our expectation: Transfer of an untested blastocyst results in a live birth of about 40-50% each transfer, with a miscarriage risk dependent on the mother’s age. However, your chances are better with a genetically normal, euploid blastocyst which results in pregnancy about 65% of the time with a 10% chance of miscarriage. Transferring two embryos, surprisingly, does not increase the live birth rate. Rather, it only increases the chance of a high-risk twin pregnancy. Ideally, we will only transfer one embryo for the best chance of a healthy pregnancy.

Let’s do the math!

So, we’ve set out our expectations for an IVF cycle, now let’s put the math to work in a hypothetical example with a woman who is under 35 with normal ovarian reserve.

Let’s say that at her egg retrieval ultrasound she has 30 follicles over 16mm. Our expectation is that of those 30 follicles, 80% will have eggs in them, leaving her with 24 eggs. Of those 24 eggs, our expectation is that 80% of these eggs will be mature and able to be fertilized. She now has 19 mature eggs ready for fertilization.

At fertilization, 80% of these eggs fertilized normally, so she now has 15 fertilized eggs ready to be cultured and grown to blastocyst stage. But only 40% of her fertilized eggs make it to 5 days, leaving her now with 6 blastocysts ready to biopsy for PGT analysis. After biopsy, 4 embryos test euploid and are ready for transfer in separate single embryo transfer procedures. Each transfer of a euploid embryo gives her a 60-70% chance of conceiving. And, after 4 separate transfers, she could hypothetically have between 2 and 3 children born through IVF.