If Dr. Springer has suggested that in-vitro fertilization and embryo transfer might be you best option to conceive a baby, then this section of our website is intended to help you understand some of the essentials of the IVF process.
Quite simply, IVF is a process where a woman’s ovaries are stimulated by a series of hormone shots which cause the ovaries to produce multiple eggs. In a normal menstrual cycle the body only produces one mature egg. When the eggs are matured they are “harvested” or “retrieved” from the ovaries. This is done by a minor surgical procedure inserting a needle through the vagina with ultrasound guidance.
After the eggs are retrieved, the embryologist prepares them for fertilization which is accomplished by inseminating or injecting the partner’s sperm directly into the eggs. The eggs are checked the next day to see how many successfully fertilized they are then placed in incubators and left undisturbed for either 3 or 5 days at which time they are evaluated for quality. In most cases all top quality embryos are then frozen and transferred back into the patient a month or so later. In some instances a fresh transfer is performed 3 days after the retrieval.
IVF was developed in the late 1970’s for the treatment of severe tubal disease. Infections, inflammations, or endometriosis may cause irreparable damage to the fallopian tubes. Since the fallopian tube is the only place in the female body where normal fertilization can occur, if both tubes become blocked, pregnancy becomes difficult or impossible. IVF allows for successful fertilization outside the fallopian tube, specifically, in the laboratory, thus bypassing the problem area. Tubal disease remains a very common indication for IVF.
Our office still gets occasional phones calls asking the best way to get pregnant following a tubal ligation. In the days prior to IVF, the only possibility for pregnancy after a tubal ligation was microscopic surgical tubal reversal, a procedure taking several hours to perform, requiring an inpatient stay, and having a recovery of several weeks. It was rarely covered by insurance. Although there is still an occasional patient for whom tubal re-anastomosis may be a reasonable choice, it has been largely replaced by IVF which offers better success rates with lower costs and a much quicker recovery.
Another common indication for IVF is low sperm counts. Because IVF allows us to super concentrate sperm or even inject it directly into the egg, we are able to achieve successful fertilization in couples who could never achieve it with intercourse or inseminations.
Infertility is said to be “unexplained” when all testing is normal, yet a couple is still unable to conceive as child. When infertility does not respond to traditional treatments such as combinations of fertility pills or shots and intrauterine inseminations, IVF can be an option.
Patients often ask why it is necessary to produce multiple eggs for a successful IVF cycle when “it only takes one”. It is important to understand that even the most fertile of patients have many poor quality eggs in their ovaries. Perhaps only 1 in every 3-4 are capable of being fertilized and growing into a term infant. For infertility patients the ratio is often much worse, maybe one in every 5 to 10. So essentially, to a degree, the more eggs we are able to stimulate to maturity, the more likely that a few of them will be good quality.
Here is an example I often use, and remember this is just an example, the exact numbers probably won’t apply specifically to you. Let’s imagine that we have a quality stimulation cycle and a patient produces 16 follicles visible on ultrasound. It is quite likely that after retrieval we will discover that only a portion of those will be mature follicles; ones that can be fertilized. So now we are down from 16 to 12 or so. Our typical successful fertilization rate is about 75% to 80% so now we have maybe 9 normal fertilized. After growing these follicles in culture for 5 days we will be fortunate to have 3 to 4 excellent quality embryos. And only half or so of these will implant and grow to a term infant.
See the problem? Remember, this is only an example. The numbers can change and do so drastically.
Dr. Springer has a saying, “all IVF begins on day 3”. By this he means that in order to get the maximum number of quality eggs it’s important to start the stimulation injections on day 3 of the menstrual cycle. This can present a problem, however, in order to allow for time to clean the lab, maintain quality control and give some downtime for our staff, the IVF lab is only open 2 to 3 weeks each month. This puts a limit to the number of days we can start our patients on stimulation each month. Obviously, everybody’s Day 3 is not going to fall into the correct window, so we can’t rely on the onset on a spontaneous period to start all of our patients.
Fortunately there is simple way to alleviate this problem. By having our patients start birth control pills on or near day 3 of any menstrual cycle, we can hold them at this stage until our next scheduled stim start. When the timing is right to start a stim cycle we have them stop their pills 5 days before their start date, which essentially puts them at day 3 of their cycle.
During this very important phase of the IVF cycle, our patients receive daily injections of Gonadotropins – hormones which stimulate the ovaries to produce multiple eggs. In a normal menstrual cycle a woman will release only one egg. Given the fact that only a small percentage of any woman’s eggs are of good quality, the ability to produce multiple eggs in an IVF cycle greatly increases the chance of retrieving one or more quality eggs. The common names for the drugs we most commonly use are Follistim, Menopur, and Ganirelix. This “stim” phase of the cycle usually lasts from between 8 days and 12 days.
Our staff will make frequent references to you about your follicles, how many and the size of each. Most of these follicles contain an egg. The eggs are very small and cannot be seen on ultrasound, but the fluid which surrounds each egg is large and can be easily seen on a scan. The size of the follicle correlates very nicely with the maturity of the egg and, as such, follicle size is a good determinant of egg quality. The larger the follicle, the nearer the egg to being ripe (mature) and ready for harvest – a procedure we refer to as follicle aspiration or egg retrieval. The egg within the follicle is usually mature and ready for aspiration when it measures 15mm or more. Before the start of stimulation the follicles are small and Estradiol (Estrogen) levels are low. Soon after starting your medication, the follicles start to grow and, usually, within 8 to 10 days the majority are 15mm or larger. During this time your follicle growth and estrogen levels will be monitored frequently by ultrasounds and blood tests.
One of the problems in the early days of IVF was that the dramatic rise in estradiol levels would occasionally cause early ovulation, or release, of the eggs. This would necessitate cancelling the cycle and starting over again the next month, a very disappointing scenario. Over the years we have utilized different medications to help prevent this premature ovulation. Currently we use a medication called Ganirelix near the latter part of the stim cycle. It has been very successful in preventing premature ovulation.
Finally the day will come when dr. Springer will determine that the eggs are “ready” for retrieval. Although there are always exceptions, his guideline is two or more follicles 19mm or greater and half or more of all the follicles 15mm or greater. If he is anticipating a fresh transfer he prefers estradiol levels under 3000 and progesterone levels under 2.0. You will then be instructed to take a so called “trigger” shot that evening. The trigger is a medication which will cause the eggs to go through their final maturation process so that they will be ready for fertilization. The trigger shot may be HCG or Leuprolide Acetate (Lupron). (More on this later) You will be instructed to take your trigger shot 35 hours prior to your scheduled egg retrieval.
The egg retrieval is a minor surgical procedure performed by inserting a needle through the vagina into the ovaries via ultrasound guidance. You will receive an anesthetic for the procedure and will experience no pain at all. The eggs are aspirated from the follicular fluid and handed to our embryologist who then prepares them for fertilization. The procedure usually takes no more than 30 minutes. Most patients are awakened shortly after the procedure and go home within the hour.
Although, most will follicles contain an egg, it not unusual for one or more of the follicles to be “empty”. Additionally, the eggs in the smaller follicles (14mm or smaller) often contain immature eggs. These may not come out during the aspiration and if they do they often cannot be fertilized.
Within a few hours of retrieval our embryologist will be preparing to fertilize the eggs with your partner’s sperm. This may be done with either traditional IVF or ICSI (intracytoplasmic sperm injection). With ICSI the embryologist actually secures a single sperm and injects it into the eggs. We have had excellent results with this procedure. Following ICSI or traditional insemination the eggs will be placed in an incubator and examined the next morning for successful fertilization. Our fertilization averages around 80% but can range from 0 to 100.
What happens next depends, to a great degree, on how many eggs are fertilized. When we have 4 or 5 or more normal fertilized eggs our preferred protocol is to keep them in the incubator undisturbed for 5 days. At that point we will take them out and examine them and then freeze all the quality embryos. We only freeze the high quality embryos and, as such, far fewer embryos are frozen than we start with.
If we have 4 or fewer eggs fertilized we often choose to perform a fresh Day #3 transfer. The best two embryos will be chosen on Day 3 and transferred into your uterus.
For those patients who have their embryos frozen, they will not have a fresh transfer. We will allow them to get the medications and high estrogen levels out of their system. This only takes a few weeks. We will then gently prepare their uterus for a transfer of a single embryo which will take place approximately a month after retrieval.
Our decision to freeze all embryos and perform a delayed embryo transfer on many of our patients is a fairly recent change in our practice. Dr. Springer has written a separate blog available on this website to further discuss this matter.
The embryo transfer itself is relatively easy much like a pap smear and requires no anesthesia. Dr. Springer will spend several minutes cleaning your cervix and making certain that the embryo can be transferred easily. Once this is accomplished our embryologist will bring the embryo into the transfer room in a small, very fine catheter. Dr. Springer will then place the embryo in the upper portion of your uterus. All of this will be done under ultrasound guidance to ensure the embryo is place in the exact perfect position. You and your partner will be able to watch the transfer on the ultrasound monitor. Immediately following the transfer you will be allowed to change and go home. Detailed instructions will be given to you regarding activity and medications for the next few days.