IN VITRO FERTILIZATION (IVF)

So you have tried “conventional” therapy for some time and have not been successful. You may have been treated with fertility drugs, undergone artificial insemination, or you may have had laparoscopy to treat scar tissue, fibroids or endometriosis. For one reason or another the egg and sperm are just not able to “meet “or implant in the uterus. The problem may be traced to tubal function, pelvic adhesions or scar tissue preventing release of the egg from the ovary. It is also possible that the sperm can not get into the egg because of low sperm count or structure or thickened egg shell. What can be done now?

What is IVF?

IVF is simply a process of fertilizing an egg with a sperm in the laboratory (in vitro) to form an embryo. The embryos are then transferred into the uterus to initiate a pregnancy.

What to expect before starting your IVF cycle

You may have already completed most of the required testing with your initial fertility evaluation. Your nurse will go over your file and will let you know what else may need to be done. The following tests may be ordered:

You will be required to have an HSG (hysterosalpingogram) within the past 2 years.
Your husband will have a semen analysis to assess the concentration, motility and morphology, and a semen culture to check for the presence of bacteria.
Your uterine cavity will be evaluated by Saline Infusion Sonography (SIS) to make sure there are no abnormalities such as uterine polyps or fibroids which may interfere with implantation.
A trial transfer will be performed at the time of the SIS to measure the depth of the uterine cavity so that the embryos can be transferred into a predetermined location within the cavity during the actual IVF cycle.
Blood tests for you and your husband will be ordered by the doctor.

What is a Saline Infusion Sonography (SIS)?

In this test, saline is injected in to the uterus while performing vaginal ultrasound to make sure that there are no uterine abnormalities (fibroids, polyps, scar tissue or uterine malformations) which may interfere with embryo implantation. The top left picture demonstrates a normal test. The dark area, outlined in yellow, is the saline filling the uterine cavity and no abnormalities are seen. The top right ultrasound image demonstrates an abnormal uterine cavity with an irregular border caused by an endometrial polyp (outlined in red and marked by a white arrow). The test takes only a few minutes to complete and is associated with little discomfort, if any.

The trial transfer (mock transfer)

A trial transfer will be performed together with the SIS to make sure that there is not going to be a problem transferring the embryos back into the uterus. The depth of the uterine cavity (thick white line) is measured so that the embryos can be transferred into a predetermined location within the cavity during the actual IVF cycle.

THE IVF CYCLE

A typical IVF treatment consists of suppression and stimulation phases and takes about 6 weeks to complete. Your doctor will determine which stimulation protocol is best for you, taking into consideration your age, weight, cycle day 3 FSH (follicle stimulating hormone) level, previous IVF treatment and ultrasound appearance of your ovaries.

The Suppression Cycle

The most common stimulation protocols utilized for IVF are:

Long protocol – utilizing GnRH agonist such as Lupron; it is typically given after 14-21 days of oral contraceptive use, or 7 days after ovulation if no oral contraceptives are taken. The purpose of Lupron is to prevent ovarian cysts from occurring, and to block spontaneous ovulation during the stimulation cycle.

Microdose agonist protocol – In patients with high FSH levels, or previous poor response to stimulation with fertility medications, the suppression phase of the treatment is omitted. The woman is treated instead with injectable hormones to stimulate ovulation beginning on day 2 or day 3 of the menstrual cycle in combination with low dose (microdose) Lupron.

Antagonist protocol - Another option is to add GnRH antagonist, such as Ganirelix starting on day 6 of gonadotropin hormone injections or when the largest follicle reaches a size of 14 mm.

The Stimulation Cycle

Expect taking fertility hormone injections for about ten days. You will have several ultrasounds and blood tests to monitor the development of the eggs and the thickness of the uterine lining (endometrial thickness).

Day 2-3 of cycle - You will have an estradiol level and a vaginal ultrasound, before you are cleared to start treatment, to make sure your ovaries contain no cysts which can interfere with proper egg development. You will continue with Lupron injections until the day before your retrieval.
Gonadotropin injections - You will be given daily hormone injections for about 8-10 days to stimulate your ovaries to produce multiple eggs.
Day 6 of cycle (day 4 of fertility hormone injections) - An estrogen blood level is measured and the medication is adjusted up if the estrogen level is low or decreased if the estrogen level is too high.
Day 8 of cycle and after - You will have several ultrasounds and estrogen level measurements to help your doctor determine when your eggs are ready for retrieval.
Ultrasound of the ovaries (below, right) demonstrating follicles containing eggs ready for retrieval.
Ultrasound of the uterus (below, left - outlined in blue); the lining of the uterus or endometrium is outlined in orange. The endometrial thickness is greater than 8 mm (outlined in yellow) and is well prepared for the embryos when they are transferred several days later.

The HCG injection

The HCG injection is given when the follicles (containing the eggs), reach 18-20 millimeter in size and the uterine lining is at least 8mm thick. The egg retrieval will take place about 35 hours later.

The Egg Retrieval

The eggs are removed from the ovaries by a minor transvaginal ultrasound surgical technique, performed in our certified in-office operating room suite. This takes about 15 min. to complete and is done using intravenous sedation administered by our board-certified anesthesiologist.
You will be going home about 30 minutes later, but plan on taking the rest of the day off.
After the retrieval you will be receiving daily progesterone treatment (injections or suppositories) until your pregnancy test 2 weeks after the retrieval. You may also be given Tetracycline (antibiotic) and Medrol (steroidal anti inflammatory) for 4 days to help the embryos implant.

Fertilization in the laboratory

Now that your eggs have been removed from your ovaries, the next step is for the embryologist to prepare your eggs and your husband’s sperm for fertilization. In cases where the sperm cannot penetrate the egg because of low sperm count, abnormally shaped sperm or low motility, the embryologist will inject one sperm directly into each egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI.
The eggs will be checked 24 hours later to see how many of them were fertilized. You will receive daily briefing from the IVF nurse coordinator, informing you of the embryos development.

ICSI (Intracytoplasmic Sperm Injection)

Utilizing "ICSI" (pronounced "icksy"), which stands for Intracytoplasmic Sperm Injection, a single sperm is all that is needed. It can be injected, using microscopic techniques (micromanipulation), directly into an egg. In this procedure, the wife undergoes a normal IVF cycle. However, when it is time to fertilize the egg, a single sperm is drawn into a very thin-tipped glass pipette. The tip of the pipette is inserted into the egg through the egg shell (zona pellucida) and the sperm is released directly into the egg. This process is repeated for each egg. The eggs are returned to the incubator and are checked 24 hours later to see how many fertilized. About 70 - 80% of the injected eggs will fertilize normally to form a zygote.

Is ICSI for me?

When undergoing IVF you may be a candidate for ICSI:

If your partner has male factor.
If there was no fertilization in a previous IVF cycle.
If there was a poor rate of egg fertilization during your previous IVF cycle.
If only few eggs are retrieved.
In cases of unexplained infertility when it is uncertain whether or not fertilization is the problem. Sometimes “partial” ICSI is performed for diagnostic purposes. Here, only half of the eggs are injected (ICSI), and the remaining eggs are allowed to fertilize conventionally (no ICSI). If the cycle is not successful, the information gained from partial ICSI can help with your next IVF cycle. If there was normal fertilization in the non ICSI group of eggs, then ICSI may be unnecessary, significantly lowering the cost of your IVF treatment. Keep in mind also that Mother Nature may do a better job than the embryologist in the lab selecting sperm to fertilize you eggs.

Stages of Embryo Development in the Laboratory

Zygote - the fertilized egg, as it appears 16-18 hours as after fertilization, showing the male and female genetic material (pronuclei) is called a zygote. Sometimes more than one sperm can penetrate the egg resulting in an abnormal zygote which will not be transferred into the uterus.

8 cell stage embryo - as it appears 72-80 hours after fertilization. Generally, 2 embryos will be transferred into the uterine cavity. If more than 3 such embryos are available, your doctor may choose to allow them to grow two more days in the laboratory to a blastocyst stage. At BocaFertility transfer of two blastocysts on day 5 results in an overall delivery rate exceeding 50%.

Blastocyst - the embryo as it appears five days after fertilization. The embryo is beginning to hatch out of its soft shell (white arrow) and is ready to implant. Since implantation rate for blastocysts is significantly higher than day 3 embryos, only 2 blastocysts need to be transferred minimizing the risk of multiple pregnancies. In selected good prognosis patients (under 35 with good quality embryos) - a single embryo transfer (SET) may be considered.

Preimplantation Genetic Diagnosis (PGD)

Preimplantation Genetic Diagnosis (PGD) is a diagnostic test for detection of chromosomal (genetic) abnormalities in the embryo during in vitro fertilization (IVF) therapy. This test however has several drawbacks, including the high-cost of the procedure, technical difficulties in performing the procedure and diagnostic limitations. With PGD, one or two cells are removed from an 8 cell embryo three days after fertilization and the cells are checked for genetic abnormalities. Only those embryos which are found to be normal are transferred into the uterus, while the abnormal ones are discarded. PGD is utilized most often in patients with genetic abnormalities, such as hemophilia or Cystic Fibrosis (CF), as a way to prevent transmitting the abnormal gene to their children. However, to date, this procedure has not been shown to be particularly helpful for patients with repeated IVF failures, older patients or patients with recurrent miscarriages. Another problem with PGD is the 1-5% false-negative (undetected abnormal embryos) and 25% false positive (normal embryos read as abnormal) results. It is often necessary to do an amniocentesis later in pregnancy to make sure that the baby is completely normal.

Before Embryo Transfer

The doctor will discuss with you the number of embryos to be implanted. In general, if you are under age 35 only one or two embryos are transferred.
Embryos are usually transferred into the uterus 3 to 5 days after fertilization.
When you have more than 3 very good quality embryos on day 3, they will most probably be kept in the incubator for 2 more days, so that they may develop into blastocysts. Not all day 3 embryos will develop into blastocysts. In fact, usually, only 50% of good quality day 3 embryos will go on to develop into blastocysts. So, if we were to predict on day 3 which embryos will continue to develop into blastocysts, we would be wrong 50% of the time. Therefore, rather than choose two embryos for transfer on day 3, it is better to wait 2 more days to see which embryos continue to develop into blastocyst stage, and select, out of those, 1 or 2 embryos for the transfer.
If less than 3 embryos are available on day 3, you will most likely be scheduled for a day 3 transfer because there is no benefit in letting the embryos continue to grow in the incubator in the laboratory and there is a risk that the embryos may not develop into blastocysts resulting in no embryo transfer at all.
In such cases incubation inside the uterus may be superior to the incubator in the laboratory.
You will be asked to sign consent forms for embryo transfer and for freezing any remaining embryos.
Prior to the transfer you will be given valium to make you feel relaxed.
You will be given a photo of the embryos being transferred for your records.

The Embryo Transfer

A speculum will be placed in your vagina. The cervix will be cleansed with culture media and the embryos will be gently transferred into a predetermined site within your womb using a very soft catheter. The transfer of the embryos is not painful and takes only a moment to accomplish. We do our transfers with your bladder empty to make it more comfortable for you. For those interested in acupuncture, arrangements can be made ahead of transfer.

Following the transfer, you will rest for 30-60 minutes before leaving the office. We recommend that you continue to take it easy at home for the next 24 hours, but it is not necessary to confine yourself to bed rest.

After the Embryo Transfer

Your pregnancy test (beta HCG) will be scheduled two weeks after your retrieval and you will be notified of the result within 1-2 hours. A positive result means that an embryo implanted and you will be instructed to continue with progesterone treatment (injections or vaginal suppositories) until the 12th week of pregnancy.

The HCG level should double every 48 hours or so in early pregnancy. A less than ideal rise in HCG level can sometimes indicate a possible miscarriage or tubal pregnancy. Therefore, your doctor may order the test every 2-3 days to make sure that the level rises appropriately.

You will be scheduled for an ultrasound about 4 weeks after your retrieval. The ultrasound will show how many embryos implanted, and display the baby’s heart rate pattern.

You will be referred to your obstetrician who will be taking care of you for the remainder of your pregnancy.

How successful is donor egg IVF?

BocaFertility has a successful donor egg IVF program achieving a pregnancy rate of about 80% and delivery rate of about 65%.

To learn more about our donor egg IVF program call us at 561-368-5500.