In Vitro Fertilization (IVF)

Drugs to stimulate the ovaries to produce multiple eggs

• Fertility Drugs for Stimulation of Egg Development: Fertility drugs are used to stimulate the development of multiple eggs during in vitro fertilization (IVF).
• Low dose hCG: The addition of very low doses of hCG to the medication protocol reduces costs and improves the stimulation of the ovaries.
• Dual Trigger with hCG and Lupron: The final injections of hCG and Lupron prepare for retrieval.

Drugs to prevent Premature ovulation

• Cetrotide and Ganirelix in IVF: Cetrotide and Ganirelix are the primary medications that help prevent premature ovulation.
• Lupron treatment in IVF: An older method for preventing ovulation.

Drugs to assist development of the uterine lining

• Progesterone supplementation: Progesterone is administered to help sustain the uterine lining (endometrium) if an immediate “fresh” transfer of an embryo is planned.

IVF Egg Retrieval (Oocyte Retrieval)

IVF egg retrieval is the process of removing eggs from the ovaries. Prior to the egg retrieval, the IVF patient will have taken fertility drugs to stimulate the development of multiple eggs.

Since IVF egg retrieval is typically performed under anesthesia, the patient must avoid having anything to eat or drink starting the night before the procedure until the morning of the IVF egg retrieval. The patient will be given a time to arrive at the Naperville Fertility Center. If fresh sperm from a partner is being used, they must also be there. While the egg retrieval procedure is underway, the partner providing the sperm will be taken to a private collection room to produce a semen specimen.

For the procedure, the patient will be given an intravenous (IV) saline drip. Through this IV, they will receive medications to allow them to sleep through the procedure. The egg retrieval is performed by passing a hollow needle through the wall of the vagina into the ovary. Using a vaginal ultrasound probe, the needle is guided to the ovary and into the follicle where the egg resides. The egg itself is not visible with the ultrasound. The fluid from the follicle is taken and deposited into a test tube. The fluid is then inspected under a microscope to find the egg.

During an average IVF stimulation, some follicles will grow to a large size and others will be medium or small. An attempt will be made to take all of the follicles, but it is not always possible to remove the egg from every follicle. Older patients, those with poor ovarian reserve, and those with smaller follicles may see a lower percentage of eggs recovered.

A good IVF egg retrieval may result in 10-20 eggs, and typically takes 15-20 minutes. Afterwards, the patient is taken to the recovery area while they recover from the anesthesia. Usually, they can leave within an hour after completing the retrieval. The couple will be told how many eggs were retrieved before they leave.

The day of the egg retrieval, the patient should plan on taking it easy, as they may be drowsy due to the residual effects of the anesthesia. Some nausea is possible, but otherwise there are no restrictions on the patient and they should be able to resume normal activities the next day.

Intracytoplasmic Sperm Injection

Intracytoplasmic Sperm Injection (ICSI) is a method used for fertilization of an egg during IVF. ICSI was first developed as a fertility treatment for couples in which the male had low sperm counts or low sperm motility. Without ICSI, these couples had a high rate of fertilization failure using standard IVF. Since its introduction, ICSI has revolutionized the treatment of male infertility. ICSI has been so successful that it is used as the fertilization method of choice for most couples.

All methods of fertilization, including ICSI, take place in a special laboratory where all conditions are sterile. The temperature and air quality in the laboratory are carefully controlled.

The eggs are removed from the ovary after the patient administers the hCG trigger injection. The hCG plays an important role; it stimulates the egg to divide into two unequal cells. The larger cell is the mature egg that will be fertilized using ICSI, and the smaller cell is called a polar body. During the egg retrieval, an attempt is made to obtain eggs from follicles of all sizes. As a result, some of the eggs will be immature and therefore cannot be fertilized. Other eggs may be degenerated or appear abnormal under the microscope. In order for an egg to be fertilized, it must be mature and healthy. Immediately after the egg retrieval, it is difficult to determine whether an egg is a mature egg. This is because each egg is covered with thousands of small cells called granulosae cells. Special enzymes are used to clear the granulosae cells away and allow clear visualization of the egg before ICSI IVF is attempted.

Next, the semen is processed to obtain an optimum sample for Intracytoplasmic Sperm Injection. Under a microscope, a single sperm is picked up using a tiny glass pipette. The sperm is injected into the egg by passing the pipette through the surface of the egg. The sperm cell is released and the pipette is withdrawn. At this time, a second polar body is released from the egg.

After the sperm cell is injected into the egg, the egg is placed into an incubator. The next morning, the injected eggs are inspected under the microscope to determine whether fertilization occurred normally. The day after the retrieval, the couple will be informed how many of the eggs fertilized normally.

Eggs are fertilized using the ICSI procedure in order to maximize the rate of fertilization and to reduce the chance for fertilization failure. In the days before ICSI, eggs were fertilized in a different manner. The egg was placed in a laboratory dish containing growth fluids. Thousands of sperm were deposited into the fluid surrounding the egg. The sperm would then need to swim to the egg, penetrate the granulosae cells, and fuse with the surface membrane of the egg in order to achieve fertilization. Studies demonstrated that about 5% of the time, fertilization would fail even if the man had a normal semen test.

Even with ICSI, occasionally fertilization does not occur or occurs abnormally. This usually happens when there are very few eggs available to inject with sperm or when the eggs are of poor quality. Ordinarily, ICSI should lead to about 70% of mature, healthy eggs fertilizing normally.

IVF Embryo Culture to the Blastocyst Stage

A blastocyst is an embryo that has been grown in the laboratory for five to six days after in vitro fertilization.

Blastocyst Formation

After fertilization has taken place, the embryos are transferred to a special growth fluid (media). The process of allowing embryos to develop in the IVF laboratory is called culturing. In order to enable the embryos to reach the blastocyst stage, the culture dishes containing the embryos and the media are maintained in an incubator where the atmosphere, humidity, and temperature are carefully monitored and controlled.

At this stage, the embryos will also be monitored for normal development. Normal embryo development requires a process of cell division called mitosis. The single fertilized egg divides into two cells, then four and so on. Some embryos will fail to divide or divide at a very slow rate, which is indicative of a poor potential for producing pregnancy. Some embryos may divide abnormally and start to fragment during their development, which also results in poor potential for producing pregnancy. By the third day after the egg retrieval, healthy eggs should have divided into eight cell embryos.

Stages of embryo development

Embryos that have only divided into two or four cell embryos by the third day have a lower potential for producing a pregnancy. Sometimes, the embryos don’t divide evenly, giving rise to embryos with three, five, or seven cells.

In addition to looking at the number of cells, embryologists will also grade the embryo by looking at its appearance under the microscope. Embryos that are dark in color or that have extensive fragmentation will also have a lower potential for producing pregnancy.

A “perfect” embryo would get a grade of 1. A poor embryo might have a grade of 3 or 4. We would like to see embryos that are 8 cells and grade 1. A patient may have a lot of good embryos or she may have none. Unfortunately, this scoring system isn’t perfect for predicting which embryos may produce a pregnancy. For this reason, some IVF programs may place more embryos into the uterus at this stage in order to increase the chances for a pregnancy. However, this increases the risk for having a multiple pregnancy.

New technology allows for time lapse imaging of embryo development. Sophisticated software can take measurements of the exact timing of certain events. Someday, as this technology improves, it may enable selection of the best embryos for transfer. For now, however, time lapse imaging is no better than an experienced embryologist.

Blastocyst Culture

Transferring embryos at the blastocyst stage will maintain the highest chance for pregnancy while keeping the risk for multiple pregnancy low. Blastocyst development requires culturing the embryos for two additional days in the laboratory. By this time (day 5 after the egg retrieval), healthy embryos will have reached the blastocyst stage.

Blastocyst Development

By definition, a blastocyst is an embryo that has divided into hundreds of cells and is composed of two parts. The outer sphere of the blastocyst is called the trophoblast. The inner portion of the blastocyst is filled with fluid. Inside the trophoblast, there is a clump of cells called the inner cell mass. The inner cell mass is the portion of the blastocyst that becomes the baby.

Blastocyst Transfer

Only a small percentage of embryos will reach the blastocyst stage. This self selection of the embryos allows the embryologist to pick the embryos that are most likely to produce a pregnancy. When transferring blastocysts, it is not necessary to transfer as many embryos to maintain a high pregnancy rate. This reduces the risk of multiple pregnancy and therefore increases the chances for a couple to have a healthy baby.

Many experts believe there is another reason for the higher pregnancy rates seen with blastocyst transfer. In a normal in vivo (in the body) conception, the embryo does not reach the uterus until the blastocyst stage. If we were to place an embryo into the uterus at the 8-cell stage (after only three days of embryo culture), it would be a deviation from normal body processes. That is, the 8 cell embryo does not belong in the uterus at that time. Transferring the embryos at the blastocyst stage is more physiologic.

Studies now demonstrate conclusively that the chance for pregnancy and the risk for multiple pregnancy are reduced with the use of blastocyst transfer. This is true for all age groups.

Embryo transfer

Embryo transfer is the process of placing embryos into the uterine cavity during an IVF procedure. Embryo transfer is a 15-minute procedure accomplished by inserting a catheter that is preloaded with embryos into the uterine cavity. At IVF1, embryo transfers are performed at the Naperville Fertility Center .

This procedure is performed under ultrasound guidance and is usually no more uncomfortable than a pap smear. Unlike most ultrasounds that are done in a fertility center, the ultrasound for an IVF embryo transfer is an abdominal ultrasound. It is therefore necessary for the patient to drink a lot of fluids so that her bladder is full. A full bladder provides an “acoustic window” that allows doctors to see the uterus more easily. It also straightens the angle between the cervix and the uterus and often makes it easier to pass a catheter into the uterus.

Occasionally, the cervical canal's structure may make it difficult to pass a catheter through. In those situations, the doctor will use a more specialized catheter that has a malleable guide wire down the center. The doctor can bend the guide wire to follow the course of the cervical canal for an easier embryo transfer.

Once the catheter tip is in place, the embryos are deposited and the catheter is removed. The embryologist will then check the catheter to ensure that the embryos have been released. Sometimes, the embryos can stick to the inside of the catheter.

After the IVF embryo transfer, the doctor can empty the bladder. The patient will then be taken to a room to rest and recover for about thirty minutes. Afterwards, the patient can return home. Although it is not required, many patients feel better if they relax that day.

There is ample evidence to suggest that bed rest after the embryo transfer does not improve the chance for pregnancy. If there is a desire to go back to work, go shopping, travel, or have intercourse that day, it is absolutely okay. No studies have been performed to investigate the effects of activities like swimming, so avoiding those activities is advised.

The embryos will be free floating in the uterus for 2-4 days after a blastocyst embryo transfer, but should then implant into the thick uterine lining. A pregnancy test is performed seven to ten days after the embryo transfer. This should be a blood test -- not a home pregnancy test -- and is mandatory even if you are sure that you are not pregnant. It is very common in IVF cycles to have bleeding or spotting after the embryo transfer. Do not stop taking your progesterone until you are instructed to do so by your provider. If the pregnancy test is positive, you will be instructed to continue taking progesterone until the 11th week of gestation, as this is important to maintain a thick uterine lining. You will also be given instructions for further monitoring.

Studies have demonstrated that the physician who performs the embryo transfer is extremely important in determining the chance for pregnancy.