IVF from start to finish
On the first day of full flow bleeding of the menstrual cycle, the patient will call us. Yes, even if it is on a weekend or holiday. She will come to the office on the second or third day for a baseline blood test and ultrasound. If a group is due to begin at that time and everything looks o.k., she will start taking fertility medications that same night. If a group is not scheduled to start, then she will start taking birth control pills until a few days before the groups is scheduled to begin.
Medications and monitoring
The first medications taken are the injections of gonadotropins medications containing FSH (Follistim or Gonal F). She will do this for four or five nights. By the fifth or sixth day of stimulation, she will return to the office for another blood test and ultrasound. By looking at her hormone levels and follicle development on ultrasound, we will decide which medications she should take, their dose and when she will come again for monitoring. This process will continue until the eggs have matured and the patient is ready for egg retrieval.
By about the fifth or sixth of stimulation, a second medication, the GnRH antagonist (Cetrotide or Ganirelix) is added to the FSH to prevent premature ovulation.
By the seventh or eighth day, on average, the dose of FSH will be decreased and replaced with low dose hCG.
The trigger injections
Most women will be ready to receive the trigger injections by the ninth or tenth day. For some, it may be as early as the seventh day and for others, as long as 16 days. The type of trigger injections given will be determined by what type of IVF cycle is being performed. If the patient is having a fresh embryo transfer, she will receive a high dose of Follistim and a high dose of hCG. If she is not having a fresh transfer, then she will take a low dose of hCG and Lupron for the trigger.
Patients who will not have a fresh transfer include women who are
- at risk for OHSS (ovarian hyperstimulation syndrome)
- freezing embryos for PGS or PGD
- freezing embryos for a deferred transfer
- egg donors
- using a gestational carrier
The egg retrieval is performed two days after the trigger injection day. During this time, antibiotic pills are given to reduce the risk of infection
Egg Retrieval and Embryo Transfer
After the egg retrieval, the woman will take one more antibiotic pill. If she is having a fresh embryo transfer, then she will also start taking progesterone. Typically, vaginal progesterone is used but in some circumstances progesterone may also be given by intramuscular injection along with supplements of oral estrogen.
If a fresh transfer is planned, it will occur on the fifth day after egg retrieval. After the embryo transfer, the progesterone is continued. A pregnancy test is performed eight days later.
Misconceptions about IVF
Recently, I have been seeing an increasing number of couples with unrealistic expectations about in vitro fertilization and cryopreservation. I have listed some of these and explained the problems in the context of an explanation of the realities of in vitro fertilization.
#1 The ultrasonographer told me she saw 20 eggs during my ultrasound!
Monitoring during an in vitro fertilization cycle includes blood tests for hormone levels and ultrasounds of the ovaries. The eggs, themselves, are too small to be seen on ultrasound. So what are the black circular areas that are seen on the ultrasound? These are the follicles. Follicles are small ovarian cysts that contain the developing eggs and fluid. As the eggs grow and mature, the follicle produces more fluid and thus the follicle gets larger. Only the follicles are seen on ultrasound, not the eggs.
#2 I counted 20 follicles on the ultrasound, I should expect 20 eggs from the egg retrieval.
During an egg retrieval, a needle is placed into the follicle and the fluid is aspirated. On the ultrasound, the doctor can see the follicle collapse around the needle. At this point, however, it is unknown whether an egg has been obtained. An embryologist inspects the fluid under the microscope to determine whether an egg has been obtained.
As an average, we are only able to get an egg out of the follicle about 70% of the time. In other words, if a patient has ten follicles aspirated, we would typically expect to get seven eggs. This is an average. Sometimes we get more, sometimes we get less. Women who commonly have lower retrieval rates include those who :
- Are older women
- Have poor ovarian reserve (high FSH levels, low AMH levels or low antral follicle counts)
- Demonstrate a poor response to fertility medications
- Have a high percentage of small follicles
- Anatomically have one or both ovaries that are difficult to reach during the retrieval
- Are obese
Occasionally, however, women who have none of the above problems may get a low yield of eggs from the retrieval.
#3 The doctor retrieved 20 eggs, that means I’ll have 20 embryos!
Initially, the eggs obtained are difficult to assess. They are covered with a large number of cells from the follicle. These cells are called cumulus cells. In order to assess the eggs clearly, these cells are stripped off the egg. Now the egg can be clearly assessed. The embryologist may find several characteristics about the eggs. The eggs can be classified as:
- Normal, healthy appearing
- Abnormal appearing
Only the healthy appearing, mature eggs will have sperm injected into them. The range of healthy mature eggs can extend from 0-100% with an average around 60%.
Once a sperm has been injected into each healthy mature egg, they are placed into an incubator overnight. The next day, the injected eggs are inspected again under the microscope. The possible things the embryologist may see include:
- An unfertilized egg
- A normally fertilized embryo
- An abnormally fertilized embryo
- Unable to determine
As an average, about 70% of the eggs that are injected will become normally fertilized. Only those eggs that are normally fertilized will be placed back into the incubator and cultured in the laboratory. The remainder will of the eggs will be discarded.
#4 I have 10 embryos, that means I will have two for transfer and 8 to freeze!
The fact is that most of the embryos created through in vitro fertilization have poor reproductive potential. The purpose behind producing a large number of embryos to enhance the ability to select the best embryos for transfer.
We inspect the embryos at two time points only. The fertilization check (1 days after the sperm was injected) and four days after the fertilization check (5 days after the sperm was injected).
Several things may be seen during the inspection of the embryos:
- An embryo may not have shown any development at all. This is known as cleavage failure.
- The embryo may be dividing, but at a rate that is slow. This is indicative of a poor quality embryo.
- The embryo may have been dividing initially, but then stopped dividing at some stage. This is known as embryonic arrest.
- The embryos may have become fragmented as they divided. This is indicative of a poor quality embryo.
- The embryos may have divided at a normal rate but appear to be of poor quality under the microscope.
- The embryo has divided at a normal rate and appears to be of normal quality under the microscope
Remember that our ability to assess an embryo strictly by looking under the microscope is very limited. There are potentially many different types of embryo abnormalities that could interfere with the embryo’s ability to produce a live born baby that will not be seen by simply looking at it under the microscope. One type of abnormality occurs when an embryo has too many or too few chromosomes. This is why chromosome testing of embryos is so valuable. However, there are other types of abnormalities that we do not have the ability to test.
However, until we have newer and better tools to help assess an embryo’s potential, the microscope remains one of the best tools to help us find embryos to transfer. We are going to transfer the most normal looking, best appearing embryos even if the rate of development or the “quality” is not as good as we would like. We will not transfer embryos that, in our opinion, are not viable.
Transferring embryos at the blastocyst stage enhances our ability to assess embryos. This is based on the fact that that only about 30% of embryos, on average, will reach the blastocyst stage. This self selection process enables us to narrow down those embryos with the best viability. This means that if a patient has 10 embryos, on average, we would expect to have two for immediate transfer and ONE embryo to freeze.
We are very selective when picking embryos for cryopreservation. Only well developed, good quality embryos will be cryopreserved. In our experience, choosing lower quality embryos results in poor survival and pregnancy rates.
In the majority of the in vitro fertilization cases that we do, couples will not have any embryos frozen. Those who do have embryos frozen, may only have one or two. It is very rare, in our program, to have a large number of embryos frozen.