IVF (in vitro fertilization) refers to the fertilization of an egg outside of the body. Any resulting embryos can be frozen for future use or transferred into a woman’s uterus in an attempt to achieve a healthy pregnancy. There are many reasons why people pursue IVF, and IVF can help circumvent many of the issues that cause infertility in men and women. In fact, as of 2014, over 1 million babies have been born via IVF in the United States. Some reasons for undergoing IVF include:
Unfortunately, IVF is a complex topic that consists of multiple steps and a lot of scientific information. However, IVF can be broken down into a few steps, which are outlined below. At Pelex, we believe that personalized care leads to optimized results, so each of our patients have their own unique treatment plans tailored to their specific needs and desires during each step of the process.
Women are born with all of the eggs that they will ever have. These millions of eggs quietly sit inside sacs, known as follicles, in the ovaries until puberty occurs. From there, women experience monthly menstrual cycles that are controlled by the production and balance of reproductive hormones from the brain and ovaries. Each cycle, multiple eggs begin to mature, but only one (sometimes two) ultimately ends up maturing while the others degenerate. This egg resides in its follicle, known as the dominant follicle, and will be ovulated during that menstrual cycle.
However, for an IVF cycle, the goal is for multiple eggs to mature so there are more eggs available for freezing or insemination and embryo development. Therefore, certain IVF medications are administered to recruit multiple eggs to mature and keep them from degenerating. These medications are administered daily beginning on days 2-4 of the menstrual cycle (though some are administered during the previous menstrual cycle). Other medications may be administered a few days later to control the timing of ovulation so that the eggs can be retrieved from the ovaries before ovulation occurs.
There are two ways to monitor how a woman’s body is responding to IVF medications:
Ultrasounds and blood tests are performed every few days once an IVF cycle begins. When the follicle measurements and blood tests indicate that the eggs are almost mature and ovulation is getting close, a trigger medication is administered to complete egg maturation and stimulate ovulation to occur.
However, ovulation cannot occur before the egg retrieval because the eggs need to be retrieved from their follicles in the ovaries. Therefore, the egg retrieval process is scheduled just prior to when ovulation should occur (~35-36 hours after the trigger shot is administered). If ovulation occurs too early, the eggs typically cannot be retrieved.
Almost all egg retrievals are performed under sedation, so pain should not be felt during the procedure. Once the sedative has begun working, the egg retrieval process begins.
The doctor uses a transvaginal ultrasound probe to see the follicles in the ovaries. At the same time, a needle connected to a small vacuum is inserted through the wall of the vagina and into the ovaries. Using the ultrasound as a guide, the doctor will pierce each follicle and aspirate (suck up) its contents. The fluid, which hopefully contains eggs, is collected in a sterile tube. An embryologist checks this fluid, isolates any eggs, and discards the remaining fluid. Once all of the follicles have been aspirated, the needle and probe are removed and a final egg count is given.
Most patients spend about 45 minutes in a recovery area after an egg retrieval as the sedative wears off. Patients are monitored and given their rules and restrictions before they leave. It is important that someone is available to drive home since it is dangerous to drive after the procedure.
In the IVF laboratory, the eggs are cleaned, graded*, and placed in an incubator until insemination occurs.
*Eggs are not graded if they are undergoing conventional insemination.
On the day of an egg retrieval, a sperm sample is either brought to (if it's fresh) or thawed at (if it's frozen) the IVF clinic. The sperm is always verified and washed prior to insemination. At Pelex, we utilize the ZyMot device for sperm washing and preparation.
There are 2 primary methods of insemination:
Insemination typically occurs a few hours after an egg retrieval procedure. After the insemination, the eggs are not checked for ~16-19 hours. After this time period, an embryologist checks to see how many eggs show signs of fertilization.
Note: it's normal for some eggs to not properly fertilize. Typically, only ~60-80% of the eggs that are inseminated will fertilize. Lower fertilization rates could indicate an egg and/or sperm quality issue or some other underlying issue.
If an egg shows signs of fertilization (it would now briefly be called a zygote), the next step is to let the embryo(s) grow inside of an incubator with a controlled environment for a few days. Unfortunately, there is no way to predict how an embryo will grow at this point.
The embryo's first step is to divide from one cell to two cells via a process known as mitosis. Those two cells will then divide into four cells, which will divide into eight cells, and so on. In normal embryo development, ~8-10 cells should be present three days after insemination occurs.
When the embryo consists of ~10-20 cells, the cells bunch together to form a morula (Latin for mulberry). This normally occurs roughly four days after insemination. As the cells continue to divide, 3 events are occurring:
Roughly 5 days after insemination, the embryo should have a relatively large blastocoel (cavity) and ~100-200 cells. However, all embryos grow at different paces. Some embryos will not have this many cells until 6 or 7 days after insemination, and some embryos will never reach this point at all.
Only embryos that are at a certain stage of development and have a certain appearance are frozen, biopsied, and/or transferred. Embryos that do not meet this criteria 5 days after insemination get another day to continue growing. If the embryos do not meet this criteria the following day, they are typically deemed unusable and are discarded.
Five days after insemination occurs, some patients will undergo a fresh embryo transfer. This requires the administration of more medications after the egg retrieval to ensure that the uterine lining is thick and ready for embryo implantation. The uterine lining will be measured prior to the embryo transfer to ensure that it is thick enough for implantation to occur.
On the morning of an embryo transfer, an embryologist will observe the patient’s embryo(s) to see how they are growing. If there is an embryo that is at the right stage/grade of development, it should be able to be transferred that day.
Most embryo transfers are not performed under sedation, though Valium may be prescribed prior to embryo transfers for calming purposes.
During an embryo transfer, the patient’s uterus will be in view using an abdominal ultrasound. The embryo(s) will be loaded into a catheter and injected into the uterus. It may be possible to see the fluid being expelled from the catheter on the ultrasound monitor. The embryologist will inspect the catheter to ensure that the embryo was successfully transferred (sometimes they stick to the wall of the catheter. If this occurs, the embryo will be reloaded and the process will repeat).
A blood test is normally scheduled ~10-14 days after an embryo transfer. Home pregnancy tests can be used, but a pregnancy should always be confirmed with a blood test. The blood test measures the level of hCG (human chorionic gonadotropin) in the blood to determine if embryo implantation has occurred. If the blood test is negative, the patient will stop taking progesterone and her period should begin a few days later. If the test is positive, the patient will schedule another blood test to ensure that the levels are rising appropriately.
In many IVF cycles, patients freeze their embryos so that they can be transferred during a later menstrual cycle. Embryos must also be frozen if they are undergoing preimplantation genetic testing (PGT, see below).
Embryos are frozen through a process known as vitrification. The embryos are moved through drops of specialized media that pull water from the embryo and protect it as it is frozen. Each frozen embryo is then placed on a small, labeled device (see picture) and quickly plunged into liquid nitrogen. Embryos can remain frozen indefinitely inside devices called cryotanks or dewars, which are monitored and filled regularly.
PGT is a technology that takes the DNA from ~5-10 of an embryo's cells and determines how many of those cells have the correct number of chromosomes (right amount of DNA). Normal cells have 23 pairs of chromosomes (one from the egg and one from the sperm).
If the embryo has the correct number of chromosomes, it has a higher chance of implanting and resulting in a healthy live birth. If the embryo does not have the correct number of chromosomes (it's abnormal), it has a high chance of either not implanting or miscarrying. Some embryos are called mosaic, meaning that they have normal and abnormal cell lines. The gender of the embryos can also be determined through PGT, if desired.
Pelex recommends PGT for patients that are over 35 years old (this is when there tends to be a higher chance of having abnormal embryos), or who have had failed IVF cycles in the past. We do not allow the transfer of abnormal embryos. Mosaic embryos can only be transferred if approved by a certified genetic counselor.
Once embryos are frozen, they need to be thawed in order to be transferred. For an embryo to thaw, it is quickly removed from the liquid nitrogen that it has been frozen in and then moved through media that safely brings the embryo to a warmer temperature. The embryo is then placed into culture fluid in an incubator, where it re-expands and resumes growing as if it was never frozen at all. Embryos are typically thawed a few hours prior to a scheduled transfer to ensure that the embryo survived the thaw and is continuing to grow.
Frozen embryo transfers are exactly like fresh embryo transfers. The only difference is that the embryo that is to be transferred is thawed a few hours prior to the transfer.